{"protocolSection":{"identificationModule":{"nctId":"NCT01794455","orgStudyIdInfo":{"id":"VR5642"},"organization":{"fullName":"Vanderbilt University","class":"OTHER"},"briefTitle":"Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression","officialTitle":"Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression"},"statusModule":{"statusVerifiedDate":"2016-08","overallStatus":"TERMINATED","whyStopped":"Enrollment difficulties","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2013-05"},"primaryCompletionDateStruct":{"date":"2015-03","type":"ACTUAL"},"completionDateStruct":{"date":"2015-03","type":"ACTUAL"},"studyFirstSubmitDate":"2013-02-12","studyFirstSubmitQcDate":"2013-02-15","studyFirstPostDateStruct":{"date":"2013-02-18","type":"ESTIMATED"},"resultsFirstSubmitDate":"2016-07-18","resultsFirstSubmitQcDate":"2016-08-26","resultsFirstPostDateStruct":{"date":"2016-10-20","type":"ESTIMATED"},"lastUpdateSubmitDate":"2016-08-26","lastUpdatePostDateStruct":{"date":"2016-10-20","type":"ESTIMATED"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Warren Taylor","investigatorTitle":"Associate Professor of Psychiatry","investigatorAffiliation":"Vanderbilt University"},"leadSponsor":{"name":"Vanderbilt University","class":"OTHER"}},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"This pilot proposal will test the hypothesis that altered cerebral vessel reactivity and cerebral hypoperfusion (decreased blood flow to the brain) is a core mechanism underlying the relationship between vascular disease and depression in older adults. The long-term objective of this line of research is to: A) determine the relationship between vascular reactivity, cerebral hypoperfusion and the persistence of late-life depression and B) determine if improving cerebral perfusion with angiotensin receptor blockers (ARBs) improves depression outcomes.","detailedDescription":"This study will examine how magnetic resonance imaging (MRI) measures of cerebral perfusion relate to antidepressant response. There are two phases to the study. In the first phase, we will examine how cerebral perfusion is related to response to sertraline, a commonly used antidepressant. In the second phase, we will examine individuals who do not respond to sertraline or other selective serotonin reuptake inhibitors (SSRI). We will examine if candesartan, an ARB, improves depression and if it does so by improving cerebral perfusion.\n\nAfter providing informed consent, participants will undergo medical and psychiatric screening. Participants determined to be eligible at the screen will proceed to a baseline evaluation, which will include brief cognitive neuropsychological testing and MRI. Participants will then begin open-label sertraline for eight weeks (baseline to week 8). Dosing will begin at 50mg daily and, based on response and tolerability, can increase up to the FDA approved maximum dose of 200mg daily.\n\nAfter the eight weeks, participants will be re-evaluated and complete another MRI. Those who respond to sertraline and experience remission of their depression will end their study participation. Those who do not experience remission will continue to the phase 2 open-label candesartan arm.\n\nThe candesartan arm will last for 12 weeks (week 8 to week 20). Dosing will begin at 4mg daily and can increase to a maximum dose of 32mg, based on tolerability and response. Participants will be monitored closely, and other antihypertensive medications adjusted to avoid low blood pressure. At the end of the 12-week trial, participants will again complete MRI and neuropsychological testing. Their study participation will then end."},"conditionsModule":{"conditions":["Depression","Hypertension"],"keywords":["Depression","Depressive Disorder","Geriatrics","Hypertension"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"NON_RANDOMIZED","interventionModel":"SINGLE_GROUP","primaryPurpose":"BASIC_SCIENCE","maskingInfo":{"masking":"NONE"}},"enrollmentInfo":{"count":1,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Phase 1: Sertraline","type":"EXPERIMENTAL","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.","interventionNames":["Drug: Sertraline"]},{"label":"Phase 2: Candesartan","type":"EXPERIMENTAL","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.","interventionNames":["Drug: Candesartan"]}],"interventions":[{"type":"DRUG","name":"Sertraline","description":"50mg - 200mg daily","armGroupLabels":["Phase 1: Sertraline"],"otherNames":["Zoloft"]},{"type":"DRUG","name":"Candesartan","description":"4mg - 32mg daily","armGroupLabels":["Phase 2: Candesartan"],"otherNames":["Atacand"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"MRI Arterial Spin Labeling","description":"MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 1 sertraline arm.","timeFrame":"Change in perfusion from baseline to week 8"},{"measure":"Montgomery Asberg Depression Rating Scale (MADRS)","description":"MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.","timeFrame":"Week 8"}],"secondaryOutcomes":[{"measure":"Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)","description":"Self-report measure of depression severity. This applies to the sertraline Phase 1 arm.","timeFrame":"Week 8"},{"measure":"Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)","description":"Self-report measure of depression severity (range 0 - 27, higher scores indicate more severe depressive symptoms). This applies to the candesartan Phase 2 arm.","timeFrame":"Week 20"},{"measure":"Montgomery-Asberg Depression Rating Scale","description":"MADRS is a measure of depression severity (range 0 - 60, higher scores indicate more severe depressive symptoms). This outcome applies to the candesartan Phase 2 arm.","timeFrame":"Week 20"},{"measure":"MRI Arterial Spin Labeling","description":"MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 2 candesartan arm.","timeFrame":"Change from week 8 to week 20"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n1. Age 60 years or older\n2. Diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic features by Diagnostic and Statistical Manual IV Text Revision (DSMIV-TR) criteria\n3. Presence of hypertension (defined as systolic \\> 140 or diastolic \\> 90 or currently receiving antihypertensive therapy)\n4. Minimum depression severity of ≥ 15 on the Montgomery-Asberg Depression Rating Scale (MADRS)\n5. Cognitively intact or with mild cognitive deficits, with a minimum score ≥ 23 on the Montreal Cognitive Assessment (MoCA).\n\nExclusion Criteria:\n\n1. Other psychiatric Axis I disorders\n2. Acute suicidality\n3. Electroconvulsive therapy in the last 6 months\n4. Primary neurological disorder, including dementia and stroke\n5. Significant cardiovascular disease, specifically diagnosis of congestive heart failure, known bilateral renal artery stenosis, symptomatic hypotension, or critical aortic or mitral stenosis\n6. Myocardial infarction or open-heart surgery in last 6 weeks\n7. Serum creatinine ≥ 265 micromol /L\n8. Serum potassium ≥ 5.5 mmol/L\n9. MRI contraindications\n10. Known allergy to sertraline or candesartan specifically or known allergy to other SSRIs or ARBs.\n11. History of prolonged (\\> 3 weeks) or self-described severe discontinuation syndrome in the past after stopping an antidepressant.\n12. Current use of an angiotensin receptor blocker\n13. Current or planned psychotherapy\n14. Need for continuous oxygen use or any medical disorder where the hypercapnia challenge would be contraindicated or put the subject at increased risk. This would include acute respiratory disease, chronic angina, or other unstable cardiac conditions.","healthyVolunteers":false,"sex":"ALL","minimumAge":"60 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Warren D Taylor, MD, MHSc","affiliation":"Vanderbilt University","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Vanderbilt Psychiatric Hospital","city":"Nashville","state":"Tennessee","zip":"37212","country":"United States","geoPoint":{"lat":36.16589,"lon":-86.78444}}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"FG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"BG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"},{"id":"BG002","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"}]}],"measures":[{"title":"Age, Categorical","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"<=18 years","categories":[{"measurements":[{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]},{"title":"Between 18 and 65 years","categories":[{"measurements":[{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]},{"title":">=65 years","categories":[{"measurements":[{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"FULL_RANGE","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG001","value":"67","lowerLimit":"67","upperLimit":"67"},{"groupId":"BG002","value":"67","lowerLimit":"67","upperLimit":"67"}]}]}]},{"title":"Gender","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"Female","categories":[{"measurements":[{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"}]}]},{"title":"Male","categories":[{"measurements":[{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"1"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"MRI Arterial Spin Labeling","description":"MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 1 sertraline arm.","populationDescription":"Could not complete MRI.","reportingStatus":"POSTED","timeFrame":"Change in perfusion from baseline to week 8","groups":[{"id":"OG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"OG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]},{"type":"PRIMARY","title":"Montgomery Asberg Depression Rating Scale (MADRS)","description":"MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.","reportingStatus":"POSTED","timeFrame":"Week 8","groups":[{"id":"OG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"OG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]},{"type":"SECONDARY","title":"Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)","description":"Self-report measure of depression severity. This applies to the sertraline Phase 1 arm.","reportingStatus":"POSTED","timeFrame":"Week 8","groups":[{"id":"OG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"OG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]},{"type":"SECONDARY","title":"Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)","description":"Self-report measure of depression severity (range 0 - 27, higher scores indicate more severe depressive symptoms). This applies to the candesartan Phase 2 arm.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"units on a scale","timeFrame":"Week 20","groups":[{"id":"OG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"OG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"1"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG001","value":"11"}]}]}]},{"type":"SECONDARY","title":"Montgomery-Asberg Depression Rating Scale","description":"MADRS is a measure of depression severity (range 0 - 60, higher scores indicate more severe depressive symptoms). This outcome applies to the candesartan Phase 2 arm.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"units on a scale","timeFrame":"Week 20","groups":[{"id":"OG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"OG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"1"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG001","value":"22"}]}]}]},{"type":"SECONDARY","title":"MRI Arterial Spin Labeling","description":"MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 2 candesartan arm.","populationDescription":"MRI data could not be obtained on the one study participant due to MRI contraindications.","reportingStatus":"POSTED","timeFrame":"Change from week 8 to week 20","groups":[{"id":"OG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily"},{"id":"OG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"12 weeks","eventGroups":[{"id":"EG000","title":"Phase 1: Sertraline","description":"Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.\n\nSertraline: 50mg - 200mg daily","seriousNumAffected":0,"seriousNumAtRisk":0,"otherNumAffected":0,"otherNumAtRisk":0},{"id":"EG001","title":"Phase 2: Candesartan","description":"For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.\n\nCandesartan: 4mg - 32mg daily","seriousNumAffected":0,"seriousNumAtRisk":1,"otherNumAffected":1,"otherNumAtRisk":1}],"otherEvents":[{"term":"Nausea","organSystem":"Gastrointestinal disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":0},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":1}]},{"term":"Fatigue","organSystem":"General disorders","assessmentType":"NON_SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":0},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":1}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"Study was ended early due to difficulty with subject recruitment. MRI data could not be obtained on that one individual due to MRI contraindications."},"certainAgreement":{"piSponsorEmployee":true},"pointOfContact":{"title":"Dr. Warren Taylor","organization":"Vanderbilt University","email":"warren.d.taylor@vanderbilt.edu","phone":"615-936-3555"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D003863","term":"Depression"},{"id":"D006973","term":"Hypertension"},{"id":"D003866","term":"Depressive Disorder"}],"ancestors":[{"id":"D001526","term":"Behavioral Symptoms"},{"id":"D001519","term":"Behavior"},{"id":"D014652","term":"Vascular Diseases"},{"id":"D002318","term":"Cardiovascular Diseases"},{"id":"D019964","term":"Mood Disorders"},{"id":"D001523","term":"Mental Disorders"}]},"interventionBrowseModule":{"meshes":[{"id":"D020280","term":"Sertraline"},{"id":"C081643","term":"candesartan"},{"id":"C077793","term":"candesartan cilexetil"}],"ancestors":[{"id":"D015057","term":"1-Naphthylamine"},{"id":"D000588","term":"Amines"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D009281","term":"Naphthalenes"},{"id":"D011084","term":"Polycyclic Aromatic Hydrocarbons"},{"id":"D006841","term":"Hydrocarbons, Aromatic"},{"id":"D006844","term":"Hydrocarbons, Cyclic"},{"id":"D006838","term":"Hydrocarbons"},{"id":"D011083","term":"Polycyclic Compounds"}]}},"hasResults":true}