{"protocolSection":{"identificationModule":{"nctId":"NCT00767624","orgStudyIdInfo":{"id":"SU-08132008-1277"},"secondaryIdInfos":[{"id":"MH78924"}],"organization":{"fullName":"Stanford University","class":"OTHER"},"briefTitle":"TRIAD - Treatment of Insomnia and Depression","officialTitle":"Improving Depression Outcome by Adding Insomnia Therapy to Antidepressants"},"statusModule":{"statusVerifiedDate":"2016-10","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2008-12"},"primaryCompletionDateStruct":{"date":"2015-06","type":"ACTUAL"},"completionDateStruct":{"date":"2015-06","type":"ACTUAL"},"studyFirstSubmitDate":"2008-10-03","studyFirstSubmitQcDate":"2008-10-06","studyFirstPostDateStruct":{"date":"2008-10-07","type":"ESTIMATED"},"resultsFirstSubmitDate":"2016-08-05","resultsFirstSubmitQcDate":"2016-10-10","resultsFirstPostDateStruct":{"date":"2016-12-05","type":"ESTIMATED"},"lastUpdateSubmitDate":"2016-10-10","lastUpdatePostDateStruct":{"date":"2016-12-05","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Rachel Manber","investigatorTitle":"Professor","investigatorAffiliation":"Stanford University"},"leadSponsor":{"name":"Stanford University","class":"OTHER"},"collaborators":[{"name":"Duke University","class":"OTHER"},{"name":"University of Pittsburgh","class":"OTHER"},{"name":"University of Pennsylvania","class":"OTHER"}]},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"The aim of the proposed three-site study is to increase the rate of full remission from major depressive disorder (MDD) at the end of 16 weeks of treatment for people who experience both major depressive disorder and insomnia.","detailedDescription":"Participants with major depressive disorder and insomnia who meet all study criteria will receive state-of-the-art antidepressant medications and one of two insomnia therapies. The specific therapy for insomnia will be determined by chance (like a flip of a coin), with an equal chance to receive either cognitive-behavioral therapy for insomnia or desensitization psychotherapy for insomnia. The study physician will select an initial antidepressant medication from a list of three possible medications . If that medication is not helpful, another medication may be tried after 8 weeks or in the event of severe side effects."},"conditionsModule":{"conditions":["Sleep Initiation and Maintenance Disorders","Depression"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2","PHASE3"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"TRIPLE","whoMasked":["PARTICIPANT","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":150,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"antidepressant + desensitization","type":"OTHER","description":"Combined antidepressant medication (determined by an algorithm) plus desensitization therapy","interventionNames":["Drug: Antidepressant","Behavioral: Desensitization Therapy for Insomnia"]},{"label":"antidepressant + cognitive behavioral","type":"OTHER","description":"Combined antidepressant medication (determined by algorithm) plus cognitive behavioral therapy","interventionNames":["Drug: Antidepressant","Behavioral: Cognitive Behavioral Therapy for Insomnia"]}],"interventions":[{"type":"DRUG","name":"Antidepressant","description":"Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance","armGroupLabels":["antidepressant + cognitive behavioral","antidepressant + desensitization"]},{"type":"BEHAVIORAL","name":"Desensitization Therapy for Insomnia","armGroupLabels":["antidepressant + desensitization"]},{"type":"BEHAVIORAL","name":"Cognitive Behavioral Therapy for Insomnia","armGroupLabels":["antidepressant + cognitive behavioral"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Percent of Participants With Depression Remission","description":"Depression remission was defined if both a and b below are satisfied\n\n1. absence of both depressed mood and anhedonia for at least three consecutive weeks\n2. no more than two other diagnostic criterion symptoms of depression met for at least three consecutive weeks","timeFrame":"16 weeks"}],"secondaryOutcomes":[{"measure":"Percentage of Participants in Insomnia Remission","description":"Remission was defined as endpoint ISI\\<8. The ISI scale score ranges from 0 to 28 with lower scores representing less severe insomnia. A score of 0-7 is interpreted as absence of insomnia.","timeFrame":"16 weeks"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n1. Meets criteria for Major Depressive Disorder\n2. Between 18 and 75 years of age and adequately fluent in English\n3. Meets criteria for an insomnia disorder\n\nExclusion Criteria:\n\n1. Women who are currently pregnant, breast-feeding, or not using a reliable birth control method.\n2. People for whom the antidepressant medication(s) provided in the study is not indicated\n3. People who have had minimum adequate trials of (or have not been able to tolerate) all three study medications.\n4. People with uncontrolled medical conditions.\n5. People with moderate or severe sleep disorders other than insomnia\n6. Individuals on a fixed night shift or rotating work schedule that requires a night shift.\n7. Patients with a current principal diagnosis of a psychiatric disorder that necessitates treatment that is not offered in the study.","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"75 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Rachel Manber","affiliation":"Stanford University","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Stanford University School of Medicine","city":"Stanford","state":"California","zip":"94305","country":"United States","geoPoint":{"lat":37.42411,"lon":-122.16608}},{"facility":"Duke University","city":"Durham","state":"North Carolina","country":"United States","geoPoint":{"lat":35.99403,"lon":-78.89862}},{"facility":"University of Pittsburgh","city":"Pittsburgh","state":"Pennsylvania","country":"United States","geoPoint":{"lat":40.44062,"lon":-79.99589}}]},"referencesModule":{"references":[{"pmid":"38183804","type":"DERIVED","citation":"Spina MA, Bei B, Rajaratnam SW, Krystal A, Edinger JD, Buysse DJ, Thase M, Manber R. Cognitive behavioural therapy for insomnia reduces actigraphy and diary measured sleep discrepancy for individuals with comorbid insomnia and major depressive disorder: A report from the TRIAD study. Sleep Med. 2024 Feb;114:137-144. doi: 10.1016/j.sleep.2023.12.014. Epub 2023 Dec 24."},{"pmid":"36798983","type":"DERIVED","citation":"Edinger JD, Smith ED, Buysse DJ, Thase M, Krystal AD, Wiskniewski S, Manber R. Objective sleep duration and response to combined pharmacotherapy and cognitive behavioral insomnia therapy among patients with comorbid depression and insomnia: a report from the TRIAD study. J Clin Sleep Med. 2023 Jun 1;19(6):1111-1120. doi: 10.5664/jcsm.10514."},{"pmid":"30952216","type":"DERIVED","citation":"Asarnow LD, Bei B, Krystal A, Buysse DJ, Thase ME, Edinger JD, Manber R. Circadian Preference as a Moderator of Depression Outcome Following Cognitive Behavioral Therapy for Insomnia Plus Antidepressant Medications: A Report From the TRIAD Study. J Clin Sleep Med. 2019 Apr 15;15(4):573-580. doi: 10.5664/jcsm.7716."},{"pmid":"29504795","type":"DERIVED","citation":"Bei B, Asarnow LD, Krystal A, Edinger JD, Buysse DJ, Manber R. Treating insomnia in depression: Insomnia related factors predict long-term depression trajectories. J Consult Clin Psychol. 2018 Mar;86(3):282-293. doi: 10.1037/ccp0000282."},{"pmid":"27788313","type":"DERIVED","citation":"Manber R, Buysse DJ, Edinger J, Krystal A, Luther JF, Wisniewski SR, Trockel M, Kraemer HC, Thase ME. Efficacy of Cognitive-Behavioral Therapy for Insomnia Combined With Antidepressant Pharmacotherapy in Patients With Comorbid Depression and Insomnia: A Randomized Controlled Trial. J Clin Psychiatry. 2016 Oct;77(10):e1316-e1323. doi: 10.4088/JCP.15m10244."}]},"ipdSharingStatementModule":{"ipdSharing":"NO"}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Antidepressant + Desensitization","description":"Combined antidepressant medication (determined by an algorithm) plus desensitization therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nDesensitization Therapy for Insomnia"},{"id":"FG001","title":"Antidepressant + Cognitive Behavioral","description":"Combined antidepressant medication (determined by algorithm) plus cognitive behavioral therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nCognitive Behavioral Therapy for Insomnia"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"75"},{"groupId":"FG001","numSubjects":"75"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"51"},{"groupId":"FG001","numSubjects":"58"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"24"},{"groupId":"FG001","numSubjects":"17"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"Intent to treat","groups":[{"id":"BG000","title":"Antidepressant + Desensitization","description":"Combined antidepressant medication (determined by an algorithm) plus desensitization therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nDesensitization Therapy for Insomnia"},{"id":"BG001","title":"Antidepressant + Cognitive Behavioral","description":"Combined antidepressant medication (determined by algorithm) plus cognitive behavioral therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nCognitive Behavioral Therapy for Insomnia"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"75"},{"groupId":"BG001","value":"75"},{"groupId":"BG002","value":"150"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"45.0","spread":"12.3"},{"groupId":"BG001","value":"48.3","spread":"12.7"},{"groupId":"BG002","value":"46.6","spread":"12.6"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"57"},{"groupId":"BG001","value":"53"},{"groupId":"BG002","value":"110"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"18"},{"groupId":"BG001","value":"22"},{"groupId":"BG002","value":"40"}]}]}]},{"title":"Insomnia Severity Index (ISI)","description":"The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. A 5-point Likert scale is used to rate each item (e.g., 0 = no problem; 4 = very severe problem), yielding a total score ranging from 0 to 28, with larger numbers representing greater severity. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8- 14); moderate insomnia (15-21); and severe insomnia (22-28).","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"18.3","spread":"3.9"},{"groupId":"BG001","value":"19.4","spread":"4.3"},{"groupId":"BG002","value":"18.9","spread":"4.1"}]}]}]},{"title":"Hamilton Rating Scale for Depression (HRSD)","description":"The HRSD is a 17-item semi-structured interview assessing the severity of depression in the past week. Items are rated on a 3 or 5 point scale. The total score is the sum of individual items, yielding a total score ranging from 0 to 52, with larger numbers representing greater severity. The total score is interpreted as follows: absence of depression (0-7); mild depression (8- 16); moderate depression (17-23); and severe depression (24-52).","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"21.5","spread":"3.7"},{"groupId":"BG001","value":"21.9","spread":"3.8"},{"groupId":"BG002","value":"21.7","spread":"3.7"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Percent of Participants With Depression Remission","description":"Depression remission was defined if both a and b below are satisfied\n\n1. absence of both depressed mood and anhedonia for at least three consecutive weeks\n2. no more than two other diagnostic criterion symptoms of depression met for at least three consecutive weeks","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of participants in arm","timeFrame":"16 weeks","groups":[{"id":"OG000","title":"Antidepressant + Desensitization","description":"Combined antidepressant medication (determined by an algorithm) plus desensitization therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nDesensitization Therapy for Insomnia"},{"id":"OG001","title":"Antidepressant + Cognitive Behavioral","description":"Combined antidepressant medication (determined by algorithm) plus cognitive behavioral therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nCognitive Behavioral Therapy for Insomnia"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"75"},{"groupId":"OG001","value":"75"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"36.0"},{"groupId":"OG001","value":"43.8"}]}]}]},{"type":"SECONDARY","title":"Percentage of Participants in Insomnia Remission","description":"Remission was defined as endpoint ISI\\<8. The ISI scale score ranges from 0 to 28 with lower scores representing less severe insomnia. A score of 0-7 is interpreted as absence of insomnia.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"percentage of particpants in arm","timeFrame":"16 weeks","groups":[{"id":"OG000","title":"Antidepressant + Desensitization","description":"Combined antidepressant medication (determined by an algorithm) plus desensitization therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nDesensitization Therapy for Insomnia"},{"id":"OG001","title":"Antidepressant + Cognitive Behavioral","description":"Combined antidepressant medication (determined by algorithm) plus cognitive behavioral therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nCognitive Behavioral Therapy for Insomnia"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"75"},{"groupId":"OG001","value":"75"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"29"},{"groupId":"OG001","value":"54"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"1","eventGroups":[{"id":"EG000","title":"Antidepressant + Desensitization","description":"Combined antidepressant medication (determined by an algorithm) plus desensitization therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nDesensitization Therapy for Insomnia","seriousNumAffected":3,"seriousNumAtRisk":75,"otherNumAffected":0,"otherNumAtRisk":75},{"id":"EG001","title":"Antidepressant + Cognitive Behavioral","description":"Combined antidepressant medication (determined by algorithm) plus cognitive behavioral therapy\n\nAntidepressant: Possible antidepressants are sertraline, escitalopram, desvenlafaxine, based on past history, response and tolerance\n\nCognitive Behavioral Therapy for Insomnia","seriousNumAffected":2,"seriousNumAtRisk":75,"otherNumAffected":1,"otherNumAtRisk":75}],"seriousEvents":[{"term":"suicidal ideation and worsening depression","organSystem":"Psychiatric disorders","notes":"Psychiatric event","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":75},{"groupId":"EG001","numAffected":1,"numAtRisk":75}]},{"term":"Worsening of known cardiac condition","organSystem":"Cardiac disorders","notes":"Medical event requiring hospitalization . Event was not expected and was not related to study meds","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":75},{"groupId":"EG001","numAffected":1,"numAtRisk":75}]},{"term":"Severe vaginal bleeding and pain","organSystem":"Reproductive system and breast disorders","notes":"Medical event requiring hospitalization.","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":75},{"groupId":"EG001","numAffected":0,"numAtRisk":75}]},{"term":"Chest pain in a patient with CAD","organSystem":"Cardiac disorders","notes":"Medical event requiring hospitalization","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":75},{"groupId":"EG001","numAffected":0,"numAtRisk":75}]},{"term":"Asthma","organSystem":"Respiratory, thoracic and mediastinal disorders","notes":"Medical event requiring hospitalization The person experiencing this event had another serious adverse event","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":75},{"groupId":"EG001","numAffected":0,"numAtRisk":75}]},{"term":"Hematoma R side abdomen","organSystem":"Blood and lymphatic system disorders","notes":"Medical event requiring hospitalization The person experiencing this event had another SAE event","stats":[{"groupId":"EG000","numAffected":1,"numAtRisk":75},{"groupId":"EG001","numAffected":0,"numAtRisk":75}]}],"otherEvents":[{"term":"Medically significant event not requiring hospitalization","organSystem":"Injury, poisoning and procedural complications","notes":"slipped on street curb and broke wrist","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":75},{"groupId":"EG001","numAffected":1,"numAtRisk":75}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"Our results do not inform clinical guidelines for any single antidepressant medication."},"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Rachel Manber, PhD","organization":"STANFORD UNIVERSITY","email":"rmanber@stanford.edu","phone":"6504981266"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D007319","term":"Sleep Initiation and Maintenance Disorders"},{"id":"D003863","term":"Depression"}],"ancestors":[{"id":"D020919","term":"Sleep Disorders, Intrinsic"},{"id":"D020920","term":"Dyssomnias"},{"id":"D012893","term":"Sleep Wake Disorders"},{"id":"D009422","term":"Nervous System Diseases"},{"id":"D001523","term":"Mental Disorders"},{"id":"D001526","term":"Behavioral Symptoms"},{"id":"D001519","term":"Behavior"}]},"interventionBrowseModule":{"meshes":[{"id":"D000928","term":"Antidepressive Agents"},{"id":"D003887","term":"Desensitization, Psychologic"},{"id":"D015928","term":"Cognitive Behavioral Therapy"}],"ancestors":[{"id":"D011619","term":"Psychotropic Drugs"},{"id":"D002491","term":"Central Nervous System Agents"},{"id":"D045506","term":"Therapeutic Uses"},{"id":"D020228","term":"Pharmacologic Actions"},{"id":"D020164","term":"Chemical Actions and Uses"},{"id":"D001521","term":"Behavior Therapy"},{"id":"D011613","term":"Psychotherapy"},{"id":"D004191","term":"Behavioral Disciplines and Activities"}]}},"hasResults":true}