{"protocolSection":{"identificationModule":{"nctId":"NCT04747314","orgStudyIdInfo":{"id":"STUDY21010105"},"secondaryIdInfos":[{"id":"UG3AR076568","type":"NIH","link":"https://reporter.nih.gov/quickSearch/UG3AR076568"}],"organization":{"fullName":"University of Pittsburgh","class":"OTHER"},"briefTitle":"Treating Negative Affect in Low Back Pain Patients","officialTitle":"Proof of Concept Study to Treat Negative Affect in Chronic Low Back Pain","acronym":"TNA-LBP"},"statusModule":{"statusVerifiedDate":"2026-08","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2021-03-31","type":"ACTUAL"},"primaryCompletionDateStruct":{"date":"2024-11-04","type":"ACTUAL"},"completionDateStruct":{"date":"2024-12-20","type":"ACTUAL"},"studyFirstSubmitDate":"2021-01-06","studyFirstSubmitQcDate":"2021-02-05","studyFirstPostDateStruct":{"date":"2021-02-10","type":"ACTUAL"},"resultsFirstSubmitDate":"2026-04-20","resultsFirstSubmitQcDate":"2026-08-24","resultsFirstPostDateStruct":{"date":"2026-08-25","type":"ACTUAL"},"lastUpdateSubmitDate":"2026-08-27","lastUpdatePostDateStruct":{"date":"2026-08-28","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR_INVESTIGATOR","investigatorFullName":"Ajay Wasan, MD, Msc","investigatorTitle":"Professor","investigatorAffiliation":"University of Pittsburgh"},"leadSponsor":{"name":"Ajay Wasan, MD, Msc","class":"OTHER"},"collaborators":[{"name":"National Institutes of Health (NIH)","class":"NIH"},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)","class":"NIH"},{"name":"Mayo Clinic","class":"OTHER"},{"name":"Massachusetts General Hospital","class":"OTHER"}]},"oversightModule":{"oversightHasDmc":true,"isFdaRegulatedDrug":true,"isFdaRegulatedDevice":false,"isUsExport":false},"descriptionModule":{"briefSummary":"This study will examine how the use of antidepressant, physical therapy, and combination of both affects pain, function, and depression outcomes in chronic low back pain patients.","detailedDescription":"Approximately 20 million Americans are affected by chronic low back pain and negative affective states such as depression and anxiety. These negative states have all been associated with higher pain intensity, lower pain tolerance, greater use of pain medication, poor pain treatment responses, and higher levels of psychiatric comorbidity among low back pain patients. To improve these outcomes for those who suffer from low back pain, it is important to implement multiple methods with a focus in treating negative affect for pain management rather than using opioids alone.\n\nAntidepressant (AD) and fear avoidance-based physical therapy (EFAR) have individually shown to be promising methods for pain management. In this study, AD, EFAR, and the combination therapy of the two treatments will be explored and implemented to investigate their effectiveness in improving pain, function, depression, and anxiety. The key innovation is testing a new and effective multimodal treatment that can help manage pain, as well as address negative affect."},"conditionsModule":{"conditions":["Chronic Low Back Pain","Negative Affectivity"],"keywords":["chronic pain","low back pain","fibromyalgia","mood","affect","depression","anxiety","opioid use"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"SEQUENTIAL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"DOUBLE","whoMasked":["CARE_PROVIDER","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":308,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Antidepressant (AD)","type":"EXPERIMENTAL","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months prescribed by a psychiatrist or an advanced practice provider supervised by a psychiatrist. During Phase 1 phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1)\n\nNon-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.","interventionNames":["Drug: Antidepressant"]},{"label":"Enhanced Fear Avoidance Rehabilitation (EFAR)","type":"EXPERIMENTAL","description":"Subjects will be randomly assigned to receive 8, 1-hour fear avoidance rehabilitation sessions conducted by a physical or occupational therapist, consisting of therapy sessions, pain education, and motivational messaging via a pain education self-help app for 4 months. Trained physical/occupational therapists will determine the activities as part of the treatment. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1).\n\nNon-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.","interventionNames":["Other: Enhanced Fear Avoidance Rehabilitation"]},{"label":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","type":"EXPERIMENTAL","description":"Subjects will receive a combination of antidepressant medication and EFAR for the first 4 months (Phase 1). In the 2nd 4 months (Phase 2) the AD treatment will be continued at the same dose(s) and they will be asked to maintain a home exercise program. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1). No re-randomization will be done in this treatment group.","interventionNames":["Drug: Antidepressant","Other: Enhanced Fear Avoidance Rehabilitation"]},{"label":"AD -> EFAR","type":"EXPERIMENTAL","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months prescribed by a psychiatrist or an advanced practice provider supervised by a psychiatrist. During Phase 1 phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1)\n\nNon-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months. Those re-randomized to EFAR for 4 months will receive 8 treatment visits. The same opioid weaning process will be followed as in Phase 1.","interventionNames":["Drug: Antidepressant","Other: Enhanced Fear Avoidance Rehabilitation"]},{"label":"EFAR -> AD","type":"EXPERIMENTAL","description":"Subjects will be randomly assigned to receive 8, 1-hour fear avoidance rehabilitation sessions conducted by a physical or occupational therapist, consisting of therapy sessions, pain education, and motivational messaging via a pain education self-help app for 4 months. Therapists will determine the activities as part of the treatment. If the patient was prescribed opioids prior to study entry, they will meet separately with a study physician to discuss possible weaning during the first 4 months (Phase 1).\n\nNon-responders at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months (Phase 2). Those re-randomized to receive AD will be prescribed medications by a psychiatrist or an advanced practice provider supervised by a psychiatrist. Phone calls every 2 weeks or in person visits will be used to evaluate the treatment and adjust the medication.\n\nThe same opioid weaning process will be followed as in Phase 1.","interventionNames":["Drug: Antidepressant","Other: Enhanced Fear Avoidance Rehabilitation"]}],"interventions":[{"type":"DRUG","name":"Antidepressant","description":"The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.","armGroupLabels":["AD -> EFAR","Antidepressant (AD)","Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","EFAR -> AD"],"otherNames":["AD: aripiprazole, bupropion, duloxetine, escitalopram, mirtazapine, sertraline, venlafaxine"]},{"type":"OTHER","name":"Enhanced Fear Avoidance Rehabilitation","description":"The EFAR treatment utilizes standardized physical and/or occupational therapy fear avoidance approaches, including pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes.","armGroupLabels":["AD -> EFAR","Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","EFAR -> AD","Enhanced Fear Avoidance Rehabilitation (EFAR)"],"otherNames":["EFAR"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"\"Composite Responder\", Involving the Domains of Pain, Function, and Depression. See \"Other Pre-Specified Outcomes\" for Description of These Sub-components.","description":"To create the \"composite responder\" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component, which simplifies the assessment of multi-domain responses. We will determine the \"composite responder\" rate of multimodal vs. single-modal treatment primarily, and then between each arm secondarily, along with the subcomponents. The \"composite responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.\n\nA participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining responses in each domain. The primary outcome is the rate of response vs. non-response on the \"Composite Responder\" measure. It will be expressed as percentiles in each category. We will also report the rate of pain+function responders and the rate of depression responders (other pre-specified outcomes).","timeFrame":"Baseline vs. 4th month of study"}],"secondaryOutcomes":[{"measure":"Change From Baseline Pain Interference at 4 Months Using PROMIS","description":"The PROMIS Short Form v1.1 - Pain Interference 4a will assess self-reported consequences of pain with 4 questions ranked on a 5-point scale, from \"not at all\" to \"very much\". The minimum raw summed score is 4 and the maximum score is 20. This is converted to a T score. A lower T-scores suggest better outcomes. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure. Outcomes will be measured and compared between the 3 treatment groups.","timeFrame":"Baseline vs. 4 months"},{"measure":"Change From Baseline Anxiety at 4 Months Using PROMIS","description":"The PROMIS Short Form v1.0 - Anxiety 4a will assess self-reported symptoms with 4 questions ranked on a 5-point scale, from \"never\" to \"always\". The minimum raw score is a 4 and the maximum is 20.. These are converted to a T score. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure. Lower T-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups.","timeFrame":"Baseline vs. 4 months"},{"measure":"Change From Baseline Sleep Disturbance at 4 Months Using PROMIS","description":"The PROMIS Short Form v1.0 - Sleep Disturbance 6a self-reported perceptions of sleep quality and sleep depth with 6 questions ranked on a 5-point scale. The minimum raw summed score is 6 and the maximum score is 30. This is converted to a T score. Lower T scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure.","timeFrame":"Baseline vs. 4 months"},{"measure":"Change From Baseline Subject's Perception of Change From Treatment at 4 Months Using Patient Global Impression of Change (PGIC)","description":"The subject's impression of the impact of the treatment on their pain and function will be measured with a 7-item scale (1 = very much worse, 2 = much worse, 3 = minimally worse, 4 = no change, 5 = minimally improved, 6 = much improved, 7 = very much improved). This is the percentage reporting \"very much improved\" or \"much improved\" at the end of Phase 1. We averaged their PGIC ratings in the 4th month.","timeFrame":"Baseline vs. 4 months"},{"measure":"Neuropathic Pain Symptoms Change, Baseline vs. 4 Months","description":"Using PainDetect, we will compare changes in neuropathic pain symptoms from baseline to 4 months. PainDetect is scored from 0-38 and based on ratings to symptom items scored from '0' (never) to '5' (very strongly). Lower scores are better.","timeFrame":"Baseline vs. 4 months"},{"measure":"Fear Avoidance Beliefs, Baseline vs. 4 Months","description":"Using the Fear Avoidance Beliefs Questionnaire, Physical Activities Items, subjects rate from '0' (completely disagree) to '6' (completely agree) five physical activities which may make their pain worse. The items are summed to produce the total score. The minimum score is a 0 and the maximum is a 30. Lower scores are better.","timeFrame":"Baseline vs. 4 months"},{"measure":"Widespread Pain Index","description":"This measure assesses the degree of widespread pain. 20 body regions are rated by patient as having pain or not. The minumum scores is a 0 and the maximum is a 20. The number of regions is summed to give the total score. Lower scores are better.","timeFrame":"Baseline vs. 4 months"},{"measure":"Change in PROMIS Fatigue Score From Baseline vs. 4 Months","description":"The PROMIS short form v. 1.0 for Fatigue consists of 2 items rated from 1-5, from \"not at all\" to \"very much.\" The minimum raw score is a 2 and the maximum is a 10. The raw score is summed and converted to a T score. Lower T scores are better. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure.","timeFrame":"Baseline vs. 4 months"},{"measure":"WPI Symptom Severity Score","description":"Overall symptom severity is rated 0-10. Lower scores are better.","timeFrame":"Baseline to 4 months"}],"otherOutcomes":[{"measure":"Change in Physical Function Using PROMIS Short Form 2.0. Function is Part of the Composite Responder Measure, and a Pain+Function Metric More Specifically. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.","description":"The PROMIS Short Form v2.0 - Physical Function 6b questionnaire will assess self-reported capability with 6 qualitatively scaled questions ranked on a 5-point scale, from \"without any difficulty\" to \"unable to do\" or \"not at all\" to \"cannot do.\" The minimum raw summed score is 6 and the maximum score is 30. Lower t-scores suggest better outcomes. A responder analysis was used as a subcomponent of the \"composite responder\" primary outcome. A \"physical function responder\" had to have at least a 3-point improvement in T score at 4 months vs. baseline. The \"physical function responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.","timeFrame":"Baseline vs. 4 months"},{"measure":"Change in Pain Intensity Using PROMIS. Pain is Part of the Composite Responder Measure, and a Pain+Function Metric More Specifically. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.","description":"The PROMIS Numeric Rating Scale v1.0 for average pain intensity-- Pain Intensity 1a questionnaire will assess how much a person hurts on average over the past 7 days, with a question ranked on a 11-point scale, from \"0 = no pain\" to \"10 = worst imaginable pain.\" The minimum raw summed score is 0 and the maximum score is 10. Lower scores suggest lower pain intensity and better outcomes. To be a \"pain responder\" a subject had to have at least 30% improvement in pain. The \"pain responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.","timeFrame":"Baseline vs. 4 months"},{"measure":"Change in Depression Using PROMIS. Depression is Part of the \"Composite Responder\" Measure. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.","description":"The PROMIS Short Form v1.0 - Depression 4a will assess self-reported negative mood and views of self with 4 questions ranked on a 5-point scale, from \"never\" to \"always\". The minimum raw summed score is 4 and the maximum score is 20. Lower T scores suggest better outcomes. A T score improvement of at least 5 points is considered a responder. The \"depression responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.","timeFrame":"Baseline vs. 4 months"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Ages 18-75\n* Pain duration \\> 6 months\n* Must meet the minimum criteria for cognitive function using the PROMIS 2-item cognitive screener (\\>3)\n* Average pain score of \\> 3/10, with low back pain being the primary pain site\n* CLBP meeting Quebec Task Force Classification System categories I-III (from axial pain only to pain radiating beyond the knee without neurological signs). Constant radicular pain associated with sensory loss is highly treatment resistant without surgery\n* In the investigator's judgment, evidence of healthcare seeking for low back pain.\n* Must meet criteria for high negative affect at 1st study visit: at least 5 on the PHQ-4 (also called the PHQ-2 + GAD-2). Scores above this level are highly associated with having a co-morbid major depression or generalized anxiety disorder diagnosis PHQ-4 scores are used as a proxy for high scores on PROMIS depression and anxiety scales\n* Having accessible electronic medical records from UPMC, Brigham and Women's Hospital, or Mayo Clinic, Rochester.\n* For those taking opioids (the opioid subgroup), participants must be prescribed opioids currently for at least 3 consecutive months prior to enrollment. Patients must be on opioids for a minimum of three months, taking them on a daily basis or intermittently during the week. The investigators will include those on strong opioids, such as oxycodone and weak opioids, such as tramadol.\n* Subject must agree that opioids cannot be increased during the study\n* For those taking opioids, no active substance use disorder in the past year as determined by the PI with the use of the Tobacco, Alcohol, Prescription Medications, and Other Substance Tool (TAPS) and a urine toxicology screen. The exceptions are tobacco, medical marijuana use in Pennsylvania or Minnesota, recreational or medical marijuana in the Boston site, or mild prescription opioid use disorder such as opioid misuse\n* No acute suicidality or history of major thought disorder (such as mania or psychosis). This will be assessed at study entry which will also include a review of history in EPIC/EMR\n* Must possess a mobile device or tablet that can send and receive text messages and access the internet\n\nExclusion Criteria:\n\n* Back surgery within the past six months\n* Active worker's compensation or litigation claims\n* New pain and/or psychiatric treatments within 2 weeks of enrollment\n* Intent to add new or increase pain treatments during the study period, such as back surgery, nerve block procedures, or medications\n* Intent to add new psychiatric treatments during the first 4 months of the study\n* Any clinically unstable systemic illness that is judged to interfere with the trial\n* History of cardiac, nervous system, or respiratory disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for respiratory depression\n* Non-ambulatory status\n* Pregnancy or the intent to become pregnant during the study. Women of childbearing potential will all submit a urine sample pregnancy testing at enrollment.\n* Not fluent in English and/or not able to complete the questionnaires","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"75 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Ajay Wasan, MD, MSc","affiliation":"University of Pittsburgh","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"BWH Pain Management Center","city":"Chestnut Hill","state":"Massachusetts","zip":"02467","country":"United States","geoPoint":{"lat":42.33065,"lon":-71.16616}},{"facility":"Mayo Clinic","city":"Rochester","state":"Minnesota","zip":"55905","country":"United States","geoPoint":{"lat":44.02163,"lon":-92.4699}},{"facility":"UPMC Pain Medicine At Centre Commons","city":"Pittsburgh","state":"Pennsylvania","zip":"15206","country":"United States","geoPoint":{"lat":40.44062,"lon":-79.99589}}]},"referencesModule":{"references":[{"pmid":"36715655","type":"DERIVED","citation":"Wasan AD, Edwards RR, Kraemer KL, Jeong J, Kenney M, Luong K, Cornelius MC, Mickles C, Dharmaraj B, Sharif E, Stoltenberg A, Emerick T, Karp JF, Bair MJ, George SZ, Hooten WM. Back Pain Consortium (BACPAC): Protocol and Pilot Study Results for a Randomized Comparative-Effectiveness Trial of Antidepressants, Fear Avoidance Rehabilitation, or the Combination for Chronic Low Back Pain and Comorbid High Negative Affect. Pain Med. 2023 Aug 4;24(Suppl 1):S105-S114. doi: 10.1093/pm/pnad006."}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Antidepressant (AD) Months 1-4","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"FG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR) Months 1-4","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"FG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR) Months 1-8","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"FG003","title":"Antidepressant → EFAR (Non-Responder Re-Randomized to EFAR) Months 5-8","description":"Only participants who agreed to be re-randomized were identified as non-responders at 4 months, were re-randomized to receive Enhanced Fear Avoidance Rehabilitation (EFAR) for an additional 4 months. EFAR included up to 8 one-hour physical therapy sessions, pain education, and activities individualized by trained therapists and focused on gradual exposure to feared movements or activities."},{"id":"FG004","title":"Antidepressant → Antidepressant (Non-Responder Re-Randomized to AD) Months 5-8","description":"Only participants who agreed to be re-randomized were identified as non-responders at 4 months, were re-randomized, continued the antidepressant treatment for an additional 4 months (total duration: 8 months), with ongoing monitoring and dose adjustment as needed."},{"id":"FG005","title":"EFAR → Antidepressant (Non-Responder Re-Randomized to AD) Months 5-8","description":"Only participants who agreed to be re-randomized and were identified as non-responders at 4 months were re-randomized to receive antidepressant (AD) treatment for an additional 4 months. Antidepressant treatment included medication management by a nurse practitioner and psychiatrist, use of the Antidepressant Treatment History Form (ATHF) and medication flowchart, check-in visits every 4 weeks, and weekly participant assessments to monitor response and tolerability."},{"id":"FG006","title":"EFAR → EFAR (Non-Responder Re-Randomized to EFAR) Months 5-8","description":"Only participants who agreed to be re-randomized were identified as non-responders at 4 months, were re-randomized to continue EFAR for an additional 4 months (total duration: 8 months)."},{"id":"FG007","title":"AD Responders Months 5-8","description":"Responders in the AD treatment will continue with the same AD treatment until the end of the study, which is month 8."},{"id":"FG008","title":"EFAR Responders - Months 5-8","description":"Responders to the EFAR treatment will continue with the same treatment and will be given an individualized home treatment program that will emphasize exercises they can perform a prescribed number of times a week during the remaining 4 months of the study."}],"periods":[{"title":"Phase 1","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","comment":"Number that received intervention as assigned","numSubjects":"100"},{"groupId":"FG001","comment":"Number that received intervention as assigned","numSubjects":"103"},{"groupId":"FG002","comment":"Number that received intervention as assigned","numSubjects":"105"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"},{"groupId":"FG005","numSubjects":"0"},{"groupId":"FG006","numSubjects":"0"},{"groupId":"FG007","numSubjects":"0"},{"groupId":"FG008","numSubjects":"0"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","comment":"Number included in analysis","numSubjects":"73"},{"groupId":"FG001","comment":"Number included in analysis","numSubjects":"68"},{"groupId":"FG002","comment":"Number included in analysis","numSubjects":"72"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"},{"groupId":"FG005","numSubjects":"0"},{"groupId":"FG006","numSubjects":"0"},{"groupId":"FG007","numSubjects":"0"},{"groupId":"FG008","numSubjects":"0"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"27"},{"groupId":"FG001","numSubjects":"35"},{"groupId":"FG002","numSubjects":"33"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"0"},{"groupId":"FG005","numSubjects":"0"},{"groupId":"FG006","numSubjects":"0"},{"groupId":"FG007","numSubjects":"0"},{"groupId":"FG008","numSubjects":"0"}]}]},{"title":"Phase 2","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","comment":"This group includes participants who agreed to re-randomization, were re-randomized to the antidepressant group, and continued participation in Phase 2 of the study under this treatment assignment.","numSubjects":"0"},{"groupId":"FG001","comment":"This group includes participants who agreed to re-randomization, were e-randomized to the EFAR group, and continued participation in Phase 2 of the study under this treatment assignment.","numSubjects":"0"},{"groupId":"FG002","comment":"This group was not re-randomized for Phase 2.","numSubjects":"72"},{"groupId":"FG003","numSubjects":"26"},{"groupId":"FG004","numSubjects":"24"},{"groupId":"FG005","numSubjects":"27"},{"groupId":"FG006","numSubjects":"24"},{"groupId":"FG007","numSubjects":"1"},{"groupId":"FG008","numSubjects":"1"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"55"},{"groupId":"FG003","numSubjects":"26"},{"groupId":"FG004","numSubjects":"19"},{"groupId":"FG005","numSubjects":"23"},{"groupId":"FG006","numSubjects":"20"},{"groupId":"FG007","numSubjects":"1"},{"groupId":"FG008","numSubjects":"1"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"17"},{"groupId":"FG003","numSubjects":"0"},{"groupId":"FG004","numSubjects":"5"},{"groupId":"FG005","numSubjects":"4"},{"groupId":"FG006","numSubjects":"4"},{"groupId":"FG007","numSubjects":"0"},{"groupId":"FG008","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"BG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"BG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"73"},{"groupId":"BG001","value":"68"},{"groupId":"BG002","value":"72"},{"groupId":"BG003","value":"213"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEDIAN","dispersionType":"INTER_QUARTILE_RANGE","unitOfMeasure":"Years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"52.5","lowerLimit":"42.1","upperLimit":"60.4"},{"groupId":"BG001","value":"52.9","lowerLimit":"39.6","upperLimit":"60.5"},{"groupId":"BG002","value":"46.5","lowerLimit":"36.9","upperLimit":"58.1"},{"groupId":"BG003","value":"50.0","lowerLimit":"39.2","upperLimit":"59.9"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"46"},{"groupId":"BG001","value":"51"},{"groupId":"BG002","value":"43"},{"groupId":"BG003","value":"140"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"27"},{"groupId":"BG001","value":"17"},{"groupId":"BG002","value":"29"},{"groupId":"BG003","value":"73"}]}]}]},{"title":"Ethnicity (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Hispanic or Latino","measurements":[{"groupId":"BG000","value":"5"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"6"},{"groupId":"BG003","value":"16"}]},{"title":"Not Hispanic or Latino","measurements":[{"groupId":"BG000","value":"68"},{"groupId":"BG001","value":"61"},{"groupId":"BG002","value":"62"},{"groupId":"BG003","value":"191"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"4"},{"groupId":"BG003","value":"6"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"2"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"2"},{"groupId":"BG003","value":"4"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"1"},{"groupId":"BG001","value":"2"},{"groupId":"BG002","value":"2"},{"groupId":"BG003","value":"5"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"13"},{"groupId":"BG002","value":"8"},{"groupId":"BG003","value":"35"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"51"},{"groupId":"BG001","value":"46"},{"groupId":"BG002","value":"57"},{"groupId":"BG003","value":"154"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"2"},{"groupId":"BG001","value":"4"},{"groupId":"BG002","value":"2"},{"groupId":"BG003","value":"8"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"3"},{"groupId":"BG001","value":"3"},{"groupId":"BG002","value":"1"},{"groupId":"BG003","value":"7"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"73"},{"groupId":"BG001","value":"68"},{"groupId":"BG002","value":"72"},{"groupId":"BG003","value":"213"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"\"Composite Responder\", Involving the Domains of Pain, Function, and Depression. See \"Other Pre-Specified Outcomes\" for Description of These Sub-components.","description":"To create the \"composite responder\" measure, Pain+ function changes will be 1 meaure, and the response rate to depression will be the 2nd component, which simplifies the assessment of multi-domain responses. We will determine the \"composite responder\" rate of multimodal vs. single-modal treatment primarily, and then between each arm secondarily, along with the subcomponents. The \"composite responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.\n\nA participant could be a pain+function responder, a depression responder, both, or neither. We use standard benchmarks for determining responses in each domain. The primary outcome is the rate of response vs. non-response on the \"Composite Responder\" measure. It will be expressed as percentiles in each category. We will also report the rate of pain+function responders and the rate of depression responders (other pre-specified outcomes).","populationDescription":"Number of responders in each group","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Baseline vs. 4th month of study","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"11"},{"groupId":"OG001","value":"8"},{"groupId":"OG002","value":"20"}]}]}]},{"type":"SECONDARY","title":"Change From Baseline Pain Interference at 4 Months Using PROMIS","description":"The PROMIS Short Form v1.1 - Pain Interference 4a will assess self-reported consequences of pain with 4 questions ranked on a 5-point scale, from \"not at all\" to \"very much\". The minimum raw summed score is 4 and the maximum score is 20. This is converted to a T score. A lower T-scores suggest better outcomes. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure. Outcomes will be measured and compared between the 3 treatment groups.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"T score","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"64.0","lowerLimit":"61.3","upperLimit":"67.5"},{"groupId":"OG001","value":"65.0","lowerLimit":"61.3","upperLimit":"68.0"},{"groupId":"OG002","value":"62.4","lowerLimit":"58.5","upperLimit":"68.2"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"60.2","lowerLimit":"57.0","upperLimit":"64.4"},{"groupId":"OG001","value":"61.0","lowerLimit":"57.9","upperLimit":"66.2"},{"groupId":"OG002","value":"58.5","lowerLimit":"54.8","upperLimit":"63.3"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-4.12","lowerLimit":"-6.62","upperLimit":"-0.73"},{"groupId":"OG001","value":"-2.41","lowerLimit":"-5.16","upperLimit":"-0.24"},{"groupId":"OG002","value":"-3.79","lowerLimit":"-7.21","upperLimit":"-0.68"}]}]}]},{"type":"SECONDARY","title":"Change From Baseline Anxiety at 4 Months Using PROMIS","description":"The PROMIS Short Form v1.0 - Anxiety 4a will assess self-reported symptoms with 4 questions ranked on a 5-point scale, from \"never\" to \"always\". The minimum raw score is a 4 and the maximum is 20.. These are converted to a T score. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure. Lower T-scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"T score","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"62.6","lowerLimit":"57.6","upperLimit":"66.2"},{"groupId":"OG001","value":"63.0","lowerLimit":"59.5","upperLimit":"68.5"},{"groupId":"OG002","value":"63.5","lowerLimit":"58.6","upperLimit":"68.4"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"55.8","lowerLimit":"52.4","upperLimit":"61.2"},{"groupId":"OG001","value":"61.2","lowerLimit":"56.0","upperLimit":"65.2"},{"groupId":"OG002","value":"56.7","lowerLimit":"51.7","upperLimit":"61.5"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-5.27","lowerLimit":"-9.2","upperLimit":"-2.4"},{"groupId":"OG001","value":"-2.99","lowerLimit":"-5.99","upperLimit":"0.06"},{"groupId":"OG002","value":"-5.7","lowerLimit":"-11.52","upperLimit":"-1.93"}]}]}]},{"type":"SECONDARY","title":"Change From Baseline Sleep Disturbance at 4 Months Using PROMIS","description":"The PROMIS Short Form v1.0 - Sleep Disturbance 6a self-reported perceptions of sleep quality and sleep depth with 6 questions ranked on a 5-point scale. The minimum raw summed score is 6 and the maximum score is 30. This is converted to a T score. Lower T scores suggest better outcomes. Outcomes will be measured and compared between the 3 treatment groups. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"T score","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"57.5","lowerLimit":"53.6","upperLimit":"62.8"},{"groupId":"OG001","value":"58.0","lowerLimit":"54.3","upperLimit":"62.3"},{"groupId":"OG002","value":"58.5","lowerLimit":"54.4","upperLimit":"63.6"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"53.9","lowerLimit":"49.8","upperLimit":"58.1"},{"groupId":"OG001","value":"56.1","lowerLimit":"53.2","upperLimit":"60.3"},{"groupId":"OG002","value":"52.8","lowerLimit":"46.6","upperLimit":"58.8"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-3.15","lowerLimit":"-6.73","upperLimit":"0.24"},{"groupId":"OG001","value":"-0.88","lowerLimit":"-5.33","upperLimit":"1.06"},{"groupId":"OG002","value":"-3.59","lowerLimit":"-9.71","upperLimit":"-1.12"}]}]}]},{"type":"SECONDARY","title":"Change From Baseline Subject's Perception of Change From Treatment at 4 Months Using Patient Global Impression of Change (PGIC)","description":"The subject's impression of the impact of the treatment on their pain and function will be measured with a 7-item scale (1 = very much worse, 2 = much worse, 3 = minimally worse, 4 = no change, 5 = minimally improved, 6 = much improved, 7 = very much improved). This is the percentage reporting \"very much improved\" or \"much improved\" at the end of Phase 1. We averaged their PGIC ratings in the 4th month.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"27"},{"groupId":"OG001","value":"21"},{"groupId":"OG002","value":"37"}]}]}]},{"type":"SECONDARY","title":"Neuropathic Pain Symptoms Change, Baseline vs. 4 Months","description":"Using PainDetect, we will compare changes in neuropathic pain symptoms from baseline to 4 months. PainDetect is scored from 0-38 and based on ratings to symptom items scored from '0' (never) to '5' (very strongly). Lower scores are better.","populationDescription":"These are the values for this measure at 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"score on a scale","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"15.0","lowerLimit":"10.00","upperLimit":"19.0"},{"groupId":"OG001","value":"14.5","lowerLimit":"10.00","upperLimit":"21.0"},{"groupId":"OG002","value":"13.2","lowerLimit":"9.2","upperLimit":"19.0"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"13.0","lowerLimit":"6.0","upperLimit":"18.0"},{"groupId":"OG001","value":"11.0","lowerLimit":"6.0","upperLimit":"18.2"},{"groupId":"OG002","value":"9.0","lowerLimit":"5.0","upperLimit":"17.0"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-2.5","lowerLimit":"-5.5","upperLimit":"0"},{"groupId":"OG001","value":"-2.25","lowerLimit":"-7","upperLimit":"0.75"},{"groupId":"OG002","value":"-3.5","lowerLimit":"-6","upperLimit":"0.5"}]}]}]},{"type":"SECONDARY","title":"Fear Avoidance Beliefs, Baseline vs. 4 Months","description":"Using the Fear Avoidance Beliefs Questionnaire, Physical Activities Items, subjects rate from '0' (completely disagree) to '6' (completely agree) five physical activities which may make their pain worse. The items are summed to produce the total score. The minimum score is a 0 and the maximum is a 30. Lower scores are better.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"score on a scale","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"20.5","lowerLimit":"15.5","upperLimit":"24.0"},{"groupId":"OG001","value":"18.8","lowerLimit":"14.5","upperLimit":"22.6"},{"groupId":"OG002","value":"19.8","lowerLimit":"16.0","upperLimit":"24.0"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"17.5","lowerLimit":"13.0","upperLimit":"22.0"},{"groupId":"OG001","value":"17.0","lowerLimit":"10.0","upperLimit":"22.0"},{"groupId":"OG002","value":"14.5","lowerLimit":"10.2","upperLimit":"21.0"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-1.75","lowerLimit":"-5.38","upperLimit":"1.38"},{"groupId":"OG001","value":"-1.5","lowerLimit":"-5.62","upperLimit":"1.5"},{"groupId":"OG002","value":"-3.5","lowerLimit":"-10","upperLimit":"0"}]}]}]},{"type":"SECONDARY","title":"Widespread Pain Index","description":"This measure assesses the degree of widespread pain. 20 body regions are rated by patient as having pain or not. The minumum scores is a 0 and the maximum is a 20. The number of regions is summed to give the total score. Lower scores are better.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"score on a scale","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"5.5","lowerLimit":"3.5","upperLimit":"8.5"},{"groupId":"OG001","value":"4.5","lowerLimit":"3.5","upperLimit":"7.5"},{"groupId":"OG002","value":"5.5","lowerLimit":"3.5","upperLimit":"8.5"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"5.0","lowerLimit":"3.0","upperLimit":"8.0"},{"groupId":"OG001","value":"4.0","lowerLimit":"3.0","upperLimit":"8.0"},{"groupId":"OG002","value":"5.0","lowerLimit":"2.0","upperLimit":"7.0"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-0.5","lowerLimit":"-2","upperLimit":"0.5"},{"groupId":"OG001","value":"-0.5","lowerLimit":"-2","upperLimit":"1.5"},{"groupId":"OG002","value":"-1","lowerLimit":"-2.5","upperLimit":"0.5"}]}]}]},{"type":"SECONDARY","title":"Change in PROMIS Fatigue Score From Baseline vs. 4 Months","description":"The PROMIS short form v. 1.0 for Fatigue consists of 2 items rated from 1-5, from \"not at all\" to \"very much.\" The minimum raw score is a 2 and the maximum is a 10. The raw score is summed and converted to a T score. Lower T scores are better. The population mean is 50 and 10 points is +/- 1 standard deviation. A T score \\>60 suggests moderately elevated levels of the measure.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"T score","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"61.8","lowerLimit":"57.1","upperLimit":"66.7"},{"groupId":"OG001","value":"62.9","lowerLimit":"57.9","upperLimit":"66.5"},{"groupId":"OG002","value":"61.7","lowerLimit":"56.9","upperLimit":"68.8"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"56.3","lowerLimit":"51.0","upperLimit":"60.8"},{"groupId":"OG001","value":"59.0","lowerLimit":"54.4","upperLimit":"65.2"},{"groupId":"OG002","value":"56.7","lowerLimit":"49.3","upperLimit":"63.8"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-6.27","lowerLimit":"-10.03","upperLimit":"-0.47"},{"groupId":"OG001","value":"-2.76","lowerLimit":"-5.91","upperLimit":"0.72"},{"groupId":"OG002","value":"-4.57","lowerLimit":"-9.7","upperLimit":"-0.04"}]}]}]},{"type":"SECONDARY","title":"WPI Symptom Severity Score","description":"Overall symptom severity is rated 0-10. Lower scores are better.","populationDescription":"These are the values for this measure at Baseline and 4 months (end of Phase 1). As noted, the change from baseline was compared. Of note, the median difference between baseline and month 4 for each study arm is not the same as the difference between the medians of baseline and month 4.","reportingStatus":"POSTED","paramType":"MEDIAN","dispersionType":"Inter-Quartile Range","unitOfMeasure":"score on a scale","timeFrame":"Baseline to 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"title":"Baseline","categories":[{"measurements":[{"groupId":"OG000","value":"7.0","lowerLimit":"5.0","upperLimit":"8.0"},{"groupId":"OG001","value":"7.0","lowerLimit":"5.5","upperLimit":"8.0"},{"groupId":"OG002","value":"6.5","lowerLimit":"4.9","upperLimit":"8.0"}]}]},{"title":"Month 4","categories":[{"measurements":[{"groupId":"OG000","value":"6.0","lowerLimit":"4.0","upperLimit":"7.0"},{"groupId":"OG001","value":"6.0","lowerLimit":"5.0","upperLimit":"8.0"},{"groupId":"OG002","value":"5.0","lowerLimit":"3.0","upperLimit":"7.0"}]}]},{"title":"Difference","categories":[{"measurements":[{"groupId":"OG000","value":"-1","lowerLimit":"-2.5","upperLimit":"0.5"},{"groupId":"OG001","value":"-0.5","lowerLimit":"-1.62","upperLimit":"0.5"},{"groupId":"OG002","value":"-1.5","lowerLimit":"-2.38","upperLimit":"0"}]}]}]},{"type":"OTHER_PRE_SPECIFIED","title":"Change in Physical Function Using PROMIS Short Form 2.0. Function is Part of the Composite Responder Measure, and a Pain+Function Metric More Specifically. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.","description":"The PROMIS Short Form v2.0 - Physical Function 6b questionnaire will assess self-reported capability with 6 qualitatively scaled questions ranked on a 5-point scale, from \"without any difficulty\" to \"unable to do\" or \"not at all\" to \"cannot do.\" The minimum raw summed score is 6 and the maximum score is 30. Lower t-scores suggest better outcomes. A responder analysis was used as a subcomponent of the \"composite responder\" primary outcome. A \"physical function responder\" had to have at least a 3-point improvement in T score at 4 months vs. baseline. The \"physical function responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.","populationDescription":"This is a proportion of responders analysis, as described in more detail above.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"34","lowerLimit":"33.4","upperLimit":"39.7"},{"groupId":"OG001","value":"31","lowerLimit":"34.1","upperLimit":"39.3"},{"groupId":"OG002","value":"39","lowerLimit":"34.1","upperLimit":"42.1"}]}]}]},{"type":"OTHER_PRE_SPECIFIED","title":"Change in Pain Intensity Using PROMIS. Pain is Part of the Composite Responder Measure, and a Pain+Function Metric More Specifically. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.","description":"The PROMIS Numeric Rating Scale v1.0 for average pain intensity-- Pain Intensity 1a questionnaire will assess how much a person hurts on average over the past 7 days, with a question ranked on a 11-point scale, from \"0 = no pain\" to \"10 = worst imaginable pain.\" The minimum raw summed score is 0 and the maximum score is 10. Lower scores suggest lower pain intensity and better outcomes. To be a \"pain responder\" a subject had to have at least 30% improvement in pain. The \"pain responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.","populationDescription":"This is a responder analysis for the number of responders in each group.","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"73"},{"groupId":"OG001","value":"68"},{"groupId":"OG002","value":"72"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"22","lowerLimit":"5.5","upperLimit":"7.0"},{"groupId":"OG001","value":"15","lowerLimit":"6.0","upperLimit":"7.5"},{"groupId":"OG002","value":"32","lowerLimit":"5.0","upperLimit":"7.5"}]}]}]},{"type":"OTHER_PRE_SPECIFIED","title":"Change in Depression Using PROMIS. Depression is Part of the \"Composite Responder\" Measure. A Subject Could be a Pain+Function Responder, a Depression Responder, Both, or Neither.","description":"The PROMIS Short Form v1.0 - Depression 4a will assess self-reported negative mood and views of self with 4 questions ranked on a 5-point scale, from \"never\" to \"always\". The minimum raw summed score is 4 and the maximum score is 20. Lower T scores suggest better outcomes. A T score improvement of at least 5 points is considered a responder. The \"depression responder\" measure will be the number and percentage of participants meeting the measure in each arm in Phase 1.","populationDescription":"A responder analysis of the numbers of patient responders in each group","reportingStatus":"POSTED","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","timeFrame":"Baseline vs. 4 months","groups":[{"id":"OG000","title":"Antidepressant (AD)","description":"Subjects will be randomly assigned to receive the antidepressant medication for 4 months under the care of a nurse practitioner and psychiatrist, in addition to their current opioid prescription and weaning guidelines, if applicable. Dosage change and side effects are mitigated by check-in visits (virtually or in-person) every 4 weeks. Non-responders determined at the end of 4 months will be re-randomized to continue receiving AD or EFAR for another 4 months.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change."},{"id":"OG001","title":"Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will be randomly assigned to receive 8 1-hour physical therapy sessions, pain education, and motivational messaging via Vivify app for 4 months, in addition to their current opioid prescription and weaning guidelines, if applicable. Trained physical/occupational therapists will determine the activities as part of the treatment. Non-responders determined at the end of 4 months will be re-randomized to continue receiving EFAR or AD for another 4 months.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. Subjects will engage in gradual exposure to exercises and activities they are apprehensive about, such as standing to wash dishes."},{"id":"OG002","title":"Antidepressant (AD) + Enhanced Fear Avoidance Rehabilitation (EFAR)","description":"Subjects will receive a combination of antidepressant medication and physical therapy for 8 months, in addition to their current opioid prescription and weaning guidelines, if applicable. No re-randomization will be done in this treatment group.\n\nAntidepressant: The antidepressant treatment utilizes antidepressant medication to improve pain, function, and depression outcomes.\n\nThe Antidepressant Treatment History Form (ATHF) will be used to assess adequacy of any prior antidepressant medication treatment and to assist the decision regarding which antidepressant to start. A medication flowchart will help serve as a guideline throughout the drug selection and dosing determination. Weekly assessments completed by subjects will help determine response, tolerability, and necessity for dose adjustment or medication change.\n\nEnhanced Fear Avoidance Rehabilitation: The EFAR treatment utilizes physical therapy, pain education, and motivational messaging to improve pain, function, and depression outcomes. 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