{"protocolSection":{"identificationModule":{"nctId":"NCT01558700","orgStudyIdInfo":{"id":"STU00039556"},"organization":{"fullName":"Northwestern University","class":"OTHER"},"briefTitle":"Duloxetine in Osteoarthritis (OA) Pain","officialTitle":"Brain Morphometries in OA Patients Treated With Duloxetine"},"statusModule":{"statusVerifiedDate":"2014-12","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2012-03"},"primaryCompletionDateStruct":{"date":"2014-04","type":"ACTUAL"},"completionDateStruct":{"date":"2014-08","type":"ACTUAL"},"studyFirstSubmitDate":"2012-03-16","studyFirstSubmitQcDate":"2012-03-19","studyFirstPostDateStruct":{"date":"2012-03-20","type":"ESTIMATED"},"resultsFirstSubmitDate":"2014-12-05","resultsFirstSubmitQcDate":"2014-12-16","resultsFirstPostDateStruct":{"date":"2014-12-29","type":"ESTIMATED"},"lastUpdateSubmitDate":"2014-12-16","lastUpdatePostDateStruct":{"date":"2014-12-29","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Apkar Apkarian","investigatorTitle":"Professor","investigatorAffiliation":"Northwestern University"},"leadSponsor":{"name":"Northwestern University","class":"OTHER"},"collaborators":[{"name":"Eli Lilly and Company","class":"INDUSTRY"}]},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"This study aims to determine in people with knee Osteoarthritis (OA) if relief of pain after treatment with either duloxetine or placebo is associated with changes in brain anatomy.","detailedDescription":"This study and the hypotheses to be tested arise from work done in our group evaluating brain cortical changes in people with chronic back pain. These studies demonstrated a loss of about 1.5 cc of neocortical gray matter per year of living with the condition, not including gray matter lost due to aging. Since this original publication, more than ten studies have replicated this basic result, showing that distinct chronic pain conditions are associated with specific brain anatomical reorganization, characterized by regional decreases in grey matter density. Recently, other studies have shown that when chronic pain is completely reversed, these anatomical changes seem to at least partially reverse within the time span of 4-12 months, providing evidence for a time window for reversal of grey matter abnormalities A fundamental question that arises from these recent studies is the extent of reversibility of the brain atrophy associated with chronic pain following continuous use of a pain-relieving drug. Apkarian's lab has generated strong evidence that the brain anatomy of subjects with osteoarthritis (OA) is dramatically different from that of healthy subjects. Given that recent data show that hip replacement OA reverses brain atrophy, the investigators can now hypothesize with greater confidence that an effective analgesic should also reverse at least some of the brain atrophy observed in OA. Thus, a study in patients with chronic knee OA treated with duloxetine provides a unique opportunity to answer this question. Since OA patients in this study will have a single new agent for four months, one can directly examine the effects of treatment in relation to progression or regression of brain atrophy. One can also examine whether or not a placebo, which is thought to reflect attentional and motivational states, affects changes in atrophy, and if so, to what extent.\n\nThe investigators consider the brain atrophy in chronic pain to be an overall marker of the extent of nervous system reorganization a subject has developed while living with the condition. Animal models of various chronic pain conditions repeatedly provide evidence for this idea, showing, for example, dramatic changes in the way pain is processed in the periphery, the spinal cord, and at the level of individual neurons. The investigators presume that these changes are the same ones contributing to atrophy in human chronic pain. However, most of underlying mechanisms remain to be uncovered. In addition, humans suffering from chronic pain exhibit a large number of cognitive and emotional deficits. The investigators presume that these deficits are directly related to the brain atrophies discovered in chronic pain conditions. Unfortunately, there are no direct studies linking brain regional atrophies to cognitive abilities in chronic pain, although such preliminary studies are underway in Apkarian's lab. Thus, in addition to the answering the previous questions, the present study will also allow us to investigate the extent to which reversing atrophy corresponds to reversing plasticity at multiple levels in the nervous system, as well as whether such reversal also corresponds to improvements in cognitive and emotional abilities."},"conditionsModule":{"conditions":["Osteoarthritis"],"keywords":["osteoarthritis","pain","brain","gray matter"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"BASIC_SCIENCE","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":40,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Duloxetine","type":"EXPERIMENTAL","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.","interventionNames":["Drug: Duloxetine"]},{"label":"Sugar pill","type":"PLACEBO_COMPARATOR","description":"Matching capsule given once a day for a total of 17 weeks.","interventionNames":["Drug: Sugar pill"]}],"interventions":[{"type":"DRUG","name":"Duloxetine","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.","armGroupLabels":["Duloxetine"],"otherNames":["Cymbalta"]},{"type":"DRUG","name":"Sugar pill","description":"Matching capsule given once a day for a total of 17 weeks.","armGroupLabels":["Sugar pill"],"otherNames":["Placebo"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Change in Brain Gray Matter Volume","description":"The change in gray matter volume is evaluated by subtracting the volume after the treatment (week 16) to the volume before treatment (baseline)","timeFrame":"16 weeks compared to baseline"}],"secondaryOutcomes":[{"measure":"Change in Pain Magnitude","description":"The Western Ontario and McMaster Osteoarthritis Index (WOMAC) score change was assess by subtracting WOMAC score after treatment (week 16) to the baseline WOMAC score. WOMAC score has a range from 0 up to 96, higher score meaning worse condition. The outcome is the decrease in WOMAC scores, meaning that the higher is the decrease, the most improvement in the condition.","timeFrame":"16 weeks compared to baseline"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Age: 45-80 years\n* ACR criteria for OA including Kellgren-Lawrence radiographic OA grades II-IV\n* VAS pain score \\>5/10 within 48 hrs of the phone screen and visit 1 (Screening)\n* Knee OA for a minimum of 12 months\n* Need for daily pain medication to manage symptoms of OA\n\nExclusion Criteria:\n\nCurrently taking MAO inhibitors or any centrally acting drug for analgesia, depression\n\n* Narrow angle glaucoma\n* Uncontrolled hypertension\n* Co-existing inflammatory arthritis, fibromyalgia or other chronic pain state.\n* If a female, pregnant, trying to become pregnant, or lactating\n* Major depressive disorder\n* Substantial alcohol use or history of significant liver disease\n* Use of MAO inhibitors, triptans, serotonin precursors (tryptophan)\n* Use of potent CYP1A2 inhibitors, Thioridazine, and anti-depressants\n* Diabetes, type 1 or type 2\n* Condition in which the Investigator believes would interfere with the subject's ability to comply with study instructions, or might confound the interpretation of the study results or put the subject at undue risk\n* MRI safety necessitates the exclusion of subjects having one or more of the following:\n\n  * Metal fragments in the eye or face, or having worked previously in the metal industry\n  * Implantation of any electronic devices such as (but not limited to) cardiac pacemakers, cardiac, defibrillators, and cochlear implants or nerve stimulators.\n  * Surgery on the blood vessels of the brain\n  * Claustrophobia (fear of enclosed places)\n  * Piercings or tattoos\n  * More than 250 lbs in weight\n  * Obvious brain abnormalities","healthyVolunteers":true,"sex":"ALL","minimumAge":"40 Years","maximumAge":"80 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Thomas Schnitzer, MD, PhD","affiliation":"Northwestern University","role":"STUDY_DIRECTOR"}],"locations":[{"facility":"Northwestern University Feinberg School of Medicine","city":"Chicago","state":"Illinois","zip":"60611","country":"United States","geoPoint":{"lat":41.85003,"lon":-87.65005}}]},"referencesModule":{"references":[{"pmid":"36269595","type":"DERIVED","citation":"Leaney AA, Lyttle JR, Segan J, Urquhart DM, Cicuttini FM, Chou L, Wluka AE. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022 Oct 21;10(10):CD012157. doi: 10.1002/14651858.CD012157.pub2."},{"pmid":"27788130","type":"DERIVED","citation":"Tetreault P, Mansour A, Vachon-Presseau E, Schnitzer TJ, Apkarian AV, Baliki MN. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials. PLoS Biol. 2016 Oct 27;14(10):e1002570. doi: 10.1371/journal.pbio.1002570. eCollection 2016 Oct."}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Duloxetine","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.\n\nDuloxetine: Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week."},{"id":"FG001","title":"Sugar Pill","description":"Matching capsule given once a day for a total of 17 weeks.\n\nSugar pill: Matching capsule given once a day for a total of 17 weeks."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"19"},{"groupId":"FG001","numSubjects":"21"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"19"},{"groupId":"FG001","numSubjects":"21"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Duloxetine","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.\n\nDuloxetine: Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week."},{"id":"BG001","title":"Sugar Pill","description":"Matching capsule given once a day for a total of 17 weeks.\n\nSugar pill: Matching capsule given once a day for a total of 17 weeks."},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"19"},{"groupId":"BG001","value":"21"},{"groupId":"BG002","value":"40"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"15"},{"groupId":"BG001","value":"16"},{"groupId":"BG002","value":"31"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"5"},{"groupId":"BG002","value":"9"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"58.6","spread":"4.2"},{"groupId":"BG001","value":"58.9","spread":"8.6"},{"groupId":"BG002","value":"58.7","spread":"6.5"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"10"},{"groupId":"BG001","value":"10"},{"groupId":"BG002","value":"20"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"9"},{"groupId":"BG001","value":"11"},{"groupId":"BG002","value":"20"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"19"},{"groupId":"BG001","value":"21"},{"groupId":"BG002","value":"40"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Change in Brain Gray Matter Volume","description":"The change in gray matter volume is evaluated by subtracting the volume after the treatment (week 16) to the volume before treatment (baseline)","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"percentage of change","timeFrame":"16 weeks compared to baseline","groups":[{"id":"OG000","title":"Duloxetine","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.\n\nDuloxetine: Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week."},{"id":"OG001","title":"Sugar Pill","description":"Matching capsule given once a day for a total of 17 weeks.\n\nSugar pill: Matching capsule given once a day for a total of 17 weeks."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"},{"groupId":"OG001","value":"21"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-0.34","spread":"0.21"},{"groupId":"OG001","value":"-0.92","spread":"0.19"}]}]}]},{"type":"SECONDARY","title":"Change in Pain Magnitude","description":"The Western Ontario and McMaster Osteoarthritis Index (WOMAC) score change was assess by subtracting WOMAC score after treatment (week 16) to the baseline WOMAC score. WOMAC score has a range from 0 up to 96, higher score meaning worse condition. The outcome is the decrease in WOMAC scores, meaning that the higher is the decrease, the most improvement in the condition.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"Scores on a scale","timeFrame":"16 weeks compared to baseline","groups":[{"id":"OG000","title":"Duloxetine","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.\n\nDuloxetine: Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week."},{"id":"OG001","title":"Sugar Pill","description":"Matching capsule given once a day for a total of 17 weeks.\n\nSugar pill: Matching capsule given once a day for a total of 17 weeks."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"19"},{"groupId":"OG001","value":"21"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"8.3","spread":"6.1"},{"groupId":"OG001","value":"8.7","spread":"6.4"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","eventGroups":[{"id":"EG000","title":"Duloxetine","description":"Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.\n\nDuloxetine: Duloxetine capsule 30mg once a day for one week, then 60mg once a day for 15 weeks, then 30mg once a day for one week.","seriousNumAffected":0,"seriousNumAtRisk":19,"otherNumAffected":6,"otherNumAtRisk":19},{"id":"EG001","title":"Sugar Pill","description":"Matching capsule given once a day for a total of 17 weeks.\n\nSugar pill: Matching capsule given once a day for a total of 17 weeks.","seriousNumAffected":0,"seriousNumAtRisk":21,"otherNumAffected":6,"otherNumAtRisk":21}],"otherEvents":[{"term":"dizziness, groggy","organSystem":"Nervous system disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":4,"numAffected":4,"numAtRisk":19},{"groupId":"EG001","numEvents":3,"numAffected":3,"numAtRisk":21}]},{"term":"worsening knee pain","organSystem":"Musculoskeletal and connective tissue disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":2,"numAffected":2,"numAtRisk":19},{"groupId":"EG001","numEvents":3,"numAffected":3,"numAtRisk":21}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Apkar Vania Apkarian","organization":"Northwestern University","email":"a-apkarian@northwestern.edu","phone":"(312) 503-0404"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D010003","term":"Osteoarthritis"},{"id":"D010146","term":"Pain"}],"ancestors":[{"id":"D001168","term":"Arthritis"},{"id":"D007592","term":"Joint Diseases"},{"id":"D009140","term":"Musculoskeletal Diseases"},{"id":"D012216","term":"Rheumatic Diseases"},{"id":"D009461","term":"Neurologic Manifestations"},{"id":"D012816","term":"Signs and Symptoms"},{"id":"D013568","term":"Pathological Conditions, Signs and Symptoms"}]},"interventionBrowseModule":{"meshes":[{"id":"D000068736","term":"Duloxetine Hydrochloride"},{"id":"D000073893","term":"Sugars"}],"ancestors":[{"id":"D013876","term":"Thiophenes"},{"id":"D013457","term":"Sulfur Compounds"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D006573","term":"Heterocyclic Compounds, 1-Ring"},{"id":"D006571","term":"Heterocyclic Compounds"},{"id":"D002241","term":"Carbohydrates"}]}},"hasResults":true}