{"protocolSection":{"identificationModule":{"nctId":"NCT00744328","orgStudyIdInfo":{"id":"R01MH057102","type":"NIH","link":"https://reporter.nih.gov/quickSearch/R01MH057102"},"organization":{"fullName":"Northwestern University","class":"OTHER"},"briefTitle":"Postpartum Depression: Transdermal Estradiol Versus Sertraline","officialTitle":"Postpartum Depression: Transdermal Estradiol Versus Sertraline","acronym":"E2SERT"},"statusModule":{"statusVerifiedDate":"2018-08","overallStatus":"TERMINATED","whyStopped":"Recruitment Issues","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2008-08"},"primaryCompletionDateStruct":{"date":"2013-09","type":"ACTUAL"},"completionDateStruct":{"date":"2013-09","type":"ACTUAL"},"studyFirstSubmitDate":"2008-08-28","studyFirstSubmitQcDate":"2008-08-28","studyFirstPostDateStruct":{"date":"2008-08-29","type":"ESTIMATED"},"resultsFirstSubmitDate":"2014-10-13","resultsFirstSubmitQcDate":"2014-10-20","resultsFirstPostDateStruct":{"date":"2014-10-23","type":"ESTIMATED"},"lastUpdateSubmitDate":"2019-08-19","lastUpdatePostDateStruct":{"date":"2019-09-10","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"PRINCIPAL_INVESTIGATOR","investigatorFullName":"Katherine Wisner","investigatorTitle":"Norman and Helen Asher Professor of Psychiatry and Behavioral Sciences and Obstetrics and Gynecology; Director, Asher Center for the Study and Treatment of Depressive Disorders","investigatorAffiliation":"Northwestern University"},"leadSponsor":{"name":"Northwestern University","class":"OTHER"}},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"The purpose of this study is to determine whether estrogen patches are effective for the treatment of postpartum major depression, as compared to sertraline (Zoloft) and placebo.","detailedDescription":"This study aims to advance our therapeutic armamentarium by evaluating the efficacy of estradiol (E2) therapy for Postpartum Major Depression (PPMD), which has received minimal research attention in America. The design of the proposed study is an 8 week randomized double-blind clinical trial of SERT vs. E2 vs. Placebo. Responders enter a continuation phase with the blind intact through 6.5 months postpartum. The primary aims of this investigation are to: 1) Test the efficacy of E2 compared to placebo for the treatment of PPMD. Sertraline will be included as an active comparator. We have powered the study to test for differences among the three groups and also test for differences between the E2 and placebo group. We will test the hypothesis that E2 will be significantly more effective than placebo and that SERT will be significantly more effective than placebo. 2) Evaluate developmental outcomes in infants exposed to the disorder, PPMD, and the medications (SERT, exogenous E2 or Placebo) which may be transmitted to the infants through breastfeeding. All infants in this study will have exposure to mothers with depression. We will assess maternal depression, mother-infant serum SERT and E2 levels and relate them to mother-infant interactional quality and infant developmental outcomes on the Bayley Scales of Infant Development. These data will enhance the sophistication of risk-benefit analyses for pharmacotherapy during lactation."},"conditionsModule":{"conditions":["Postpartum Depression"],"keywords":["Postpartum depression","estradiol","Postpartum major depressive disorder"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"QUADRUPLE","whoMasked":["PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR"]}},"enrollmentInfo":{"count":85,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Transdermal Estradiol","type":"EXPERIMENTAL","description":"Women wear a skin patch that is changed weekly and take opaque capsules by mouth daily. The capsules for women in this arm do not contain any active ingredients. The skin patch contains transdermal estradiol ranging in dose from 50 to 200 mcg/day","interventionNames":["Drug: Transdermal Estradiol","Other: Placebo"]},{"label":"Sertraline","type":"ACTIVE_COMPARATOR","description":"Women wear a skin patch that is changed weekly and take opaque capsules by mouth daily. The skin patch contains no active ingredients, though packaging is designed to match active patches. The capsules contain sertraline ranging in dose from 25 to 200mg/day","interventionNames":["Drug: Sertraline","Other: Placebo"]},{"label":"Placebo","type":"PLACEBO_COMPARATOR","description":"Women wear a skin patch that is changed weekly and take opaque capsules by mouth daily. The capsules for women in this arm do not contain any active ingredients. The skin patch contains no active ingredients, though packaging is designed to match active patches.","interventionNames":["Other: Placebo"]}],"interventions":[{"type":"DRUG","name":"Transdermal Estradiol","description":"Estradiol patch ranging in dose from 50 to 200 mcg/day","armGroupLabels":["Transdermal Estradiol"],"otherNames":["Vivelle dot","Climara"]},{"type":"DRUG","name":"Sertraline","description":"Sertraline dose will range from 50 - 200 mg/day","armGroupLabels":["Sertraline"],"otherNames":["Zoloft"]},{"type":"OTHER","name":"Placebo","description":"Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.","armGroupLabels":["Placebo","Sertraline","Transdermal Estradiol"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29","description":"Depression was assessed with the Structured Interview Guide for the Hamilton Depression Rating Scale - Atypical Depression Symptoms Version (SIGH-ADS29). The scale incorporates the 17 and 21-item Hamilton Rating Scales for Depression (HRSD) as well as 8 atypical symptoms of depression. Scores range from 0 to 90, where a higher score corresponds to a higher level of depressive symptomatology.","timeFrame":"Week 8"}],"secondaryOutcomes":[{"measure":"Infant Serum Concentrations of Estradiol in 3 Treatment Arms","description":"As expected due to being stopped and therefore underpowered","timeFrame":"monthly"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Ages 18-45 years\n* Had a baby within the last 3 months\n* Experiencing depression or lasting sadness\n\nExclusion Criteria:\n\n* Current use of other therapies for depression, such as antidepressants, psychotherapy, bright light therapy, and herbal remedies such as Hypericum St. John's Wort\n* DSM-IV diagnoses of bipolar 1 or 2 disorder or any psychotic episode; substance abuse within last 6 months\n* Previous adverse reaction to sertraline or provera\n* No pediatric care: No pediatrician with whom to coordinate breastfeeding and infant care\n* Use of medications for medical disorders, except for treatment of hypothyroidism or inhalers for asthma or progestin-only contraceptives\n* Heavy smoking (\\>10 cigarettes per day) or intent to resume heavy smoking (unless willing to cut down)\n* personal history of thromboembolic event, hypercoagulability, or first degree relatives with thromboembolic events.\n* Current or past personal history of breast, uterine, or ovarian cancer.\n* BRCA-positive mother\n* Arterial vascular disease and/or heart disease: increased risk of stroke.\n* Liver disease: increased risk of biliary stones, cholestatic jaundice and benign hepatic lesions with E2 treatment.\n* Diabetes\n* Pregnancy\n* Infants born \\<32 weeks of gestation\n* Imminent suicidality and/or homicidality: in need of higher level of care than is provided in this study.","healthyVolunteers":false,"sex":"FEMALE","minimumAge":"18 Years","maximumAge":"45 Years","stdAges":["ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Katherine L Wisner, MD, MS","affiliation":"Northwestern University","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Northwestern University Feinberg School of Medicine; Asher Center for the Study and Treatment of Depressive Disorders","city":"Chicago","state":"Illinois","zip":"60611","country":"United States","geoPoint":{"lat":41.85003,"lon":-87.65005}}]},"referencesModule":{"references":[{"pmid":"39626074","type":"DERIVED","citation":"Pulido CM, Walson IS, Yang A, Stika CS, Sit DK, Wisner KL. Differentiating Depressive Symptoms From Side Effects in Individuals With Major Depressive Disorder With Postpartum Onset. J Clin Psychopharmacol. 2025 Mar-Apr 01;45(2):106-110. doi: 10.1097/JCP.0000000000001928. Epub 2024 Dec 4."},{"pmid":"22283499","type":"DERIVED","citation":"Prairie BA, Wisniewski SR, Luther JF, Sit D, Wisner KL. Postpartum lipid levels in women with major depression. J Womens Health (Larchmt). 2012 May;21(5):534-8. doi: 10.1089/jwh.2011.3256. Epub 2012 Jan 27."}],"seeAlsoLinks":[{"label":"Northwestern Psychiatry Homepage","url":"http://psychiatry.northwestern.edu"}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Estradiol","description":"Administered via skin patch ranging in dose from 50 to 200 mcg/day\n\nTransdermal Estradiol: Estradiol patch ranging in dose from 50 to 200 mcg/day"},{"id":"FG001","title":"Sertraline","description":"Administered via capsules taken orally ranging in dose from 25 to 200mg/day\n\nSertraline: Sertraline dose will range from 50 - 200 mg/day"},{"id":"FG002","title":"Placebo","description":"Placebo: Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used."}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"26"},{"groupId":"FG001","numSubjects":"30"},{"groupId":"FG002","numSubjects":"29"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"19"},{"groupId":"FG001","numSubjects":"22"},{"groupId":"FG002","numSubjects":"21"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"7"},{"groupId":"FG001","numSubjects":"8"},{"groupId":"FG002","numSubjects":"8"}]}],"dropWithdraws":[{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"2"},{"groupId":"FG001","numSubjects":"5"},{"groupId":"FG002","numSubjects":"3"}]},{"type":"Withdrawal by Subject","reasons":[{"groupId":"FG000","numSubjects":"5"},{"groupId":"FG001","numSubjects":"3"},{"groupId":"FG002","numSubjects":"4"}]},{"type":"Found ineligible after randomization","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"1"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Estradiol","description":"Administered via skin patch ranging in dose from 50 to 200 mcg/day\n\nTransdermal Estradiol: Estradiol patch ranging in dose from 50 to 200 mcg/day"},{"id":"BG001","title":"Sertraline","description":"Administered via capsules taken orally ranging in dose from 25 to 200mg/day\n\nSertraline: Sertraline dose will range from 50 - 200 mg/day"},{"id":"BG002","title":"Placebo","description":"Placebo: Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used."},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"26"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"29"},{"groupId":"BG003","value":"85"}]}],"measures":[{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"26.2","spread":"5.98"},{"groupId":"BG001","value":"26.2","spread":"5.89"},{"groupId":"BG002","value":"27.4","spread":"5.48"},{"groupId":"BG003","value":"26.6","spread":"5.74"}]}]}]},{"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"},{"groupId":"BG003","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"26"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"29"},{"groupId":"BG003","value":"85"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"26"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"29"},{"groupId":"BG003","value":"85"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]}]}]},{"title":"Race (NIH/OMB)","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"American Indian or Alaska Native","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"1"}]},{"title":"Asian","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"3"},{"groupId":"BG003","value":"3"}]},{"title":"Native Hawaiian or Other Pacific Islander","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"1"}]},{"title":"Black or African American","measurements":[{"groupId":"BG000","value":"10"},{"groupId":"BG001","value":"9"},{"groupId":"BG002","value":"4"},{"groupId":"BG003","value":"23"}]},{"title":"White","measurements":[{"groupId":"BG000","value":"14"},{"groupId":"BG001","value":"19"},{"groupId":"BG002","value":"21"},{"groupId":"BG003","value":"54"}]},{"title":"More than one race","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Unknown or Not Reported","measurements":[{"groupId":"BG000","value":"2"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"1"},{"groupId":"BG003","value":"3"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"26"},{"groupId":"BG001","value":"30"},{"groupId":"BG002","value":"29"},{"groupId":"BG003","value":"85"}]}]}]},{"title":"SIGHADS29","description":"Depression was assessed with the Structured Interview Guide for the Hamilton Depression Rating Scale - Atypical Depression Symptoms Version (SIGH-ADS29). The scale incorporates the 17 and 21-item Hamilton Rating Scales for Depression (HRSD) as well as 8 atypical symptoms of depression. Scores range from 0 to 90, where a higher score corresponds to a higher level of depressive symptomatology. A minimum SIGH-ADS29 score of 18 was required for enrollment.","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"Scores on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"23.3","spread":"4.99"},{"groupId":"BG001","value":"23.3","spread":"3.67"},{"groupId":"BG002","value":"25.1","spread":"4.92"},{"groupId":"BG003","value":"23.9","spread":"4.56"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"To Test the Efficacy of Estradiol for the Treatment of Postpartum Depression - Percent Change in SIGH-ADS29","description":"Depression was assessed with the Structured Interview Guide for the Hamilton Depression Rating Scale - Atypical Depression Symptoms Version (SIGH-ADS29). The scale incorporates the 17 and 21-item Hamilton Rating Scales for Depression (HRSD) as well as 8 atypical symptoms of depression. Scores range from 0 to 90, where a higher score corresponds to a higher level of depressive symptomatology.","populationDescription":"Analyses presented are Last Observation Carried Forward. For women who completed the 8 week trial the percent change was measured from baseline to week 8. For non-completers, the percent change was measured from baseline to last observation.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"percentage change in SIGH-ADS29 Score","timeFrame":"Week 8","groups":[{"id":"OG000","title":"Estradiol","description":"Administered via skin patch ranging in dose from 50 to 200 mcg/day\n\nTransdermal Estradiol: Estradiol patch ranging in dose from 50 to 200 mcg/day"},{"id":"OG001","title":"Sertraline","description":"Administered via capsules taken orally ranging in dose from 25 to 200mg/day\n\nSertraline: Sertraline dose will range from 50 - 200 mg/day"},{"id":"OG002","title":"Placebo","description":"Placebo: Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"26"},{"groupId":"OG001","value":"30"},{"groupId":"OG002","value":"29"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-38","spread":"33.7"},{"groupId":"OG001","value":"-49","spread":"24.1"},{"groupId":"OG002","value":"-48","spread":"29.8"}]}]}]},{"type":"SECONDARY","title":"Infant Serum Concentrations of Estradiol in 3 Treatment Arms","description":"As expected due to being stopped and therefore underpowered","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"pg/mL","timeFrame":"monthly","groups":[{"id":"OG000","title":"Estradiol","description":"Administered via skin patch ranging in dose from 50 to 200 mcg/day\n\nTransdermal Estradiol: Estradiol patch ranging in dose from 50 to 200 mcg/day"},{"id":"OG001","title":"Sertraline","description":"Administered via capsules taken orally ranging in dose from 25 to 200mg/day\n\nSertraline: Sertraline dose will range from 50 - 200 mg/day"},{"id":"OG002","title":"Placebo","description":"Placebo: Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used."}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"6"},{"groupId":"OG001","value":"6"},{"groupId":"OG002","value":"7"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"2.45","spread":"3.80"},{"groupId":"OG001","value":"2.1","spread":"3.36"},{"groupId":"OG002","value":"5.59","spread":"7.79"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Weekly during the 8-week acute phase","description":"If a patient develops a symptom score on the Mania Rating Scale of \\>10, she will receive an immediate consultation for a revised treatment regimen by non-blind medical monitor to keep primary study staff blind to pill/patch content. Occurrence of hypomania/mania will signal termination from the trial.","eventGroups":[{"id":"EG000","title":"Estradiol","description":"Administered via skin patch ranging in dose from 50 to 200 mcg/day\n\nTransdermal Estradiol: Estradiol patch ranging in dose from 50 to 200 mcg/day","seriousNumAffected":0,"seriousNumAtRisk":26,"otherNumAffected":0,"otherNumAtRisk":26},{"id":"EG001","title":"Sertraline","description":"Administered via capsules taken orally ranging in dose from 25 to 200mg/day\n\nSertraline: Sertraline dose will range from 50 - 200 mg/day","seriousNumAffected":0,"seriousNumAtRisk":30,"otherNumAffected":4,"otherNumAtRisk":30},{"id":"EG002","title":"Placebo","description":"Placebo: Placebo patches and pills that are identical to transdermal estradiol and oral sertraline, respectively, will be used.","seriousNumAffected":0,"seriousNumAtRisk":29,"otherNumAffected":1,"otherNumAtRisk":29}],"otherEvents":[{"term":"Treatment Emergent Manic Symptoms","organSystem":"Psychiatric disorders","sourceVocabulary":"Mania Rating Scale","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numAffected":0,"numAtRisk":26},{"groupId":"EG001","numAffected":4,"numAtRisk":30},{"groupId":"EG002","numAffected":1,"numAtRisk":29}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Research Study Coordinator","organization":"Northwestern University","email":"emily.pinheiro@northwestern.edu","phone":"312-695-8441"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-13"},"conditionBrowseModule":{"meshes":[{"id":"D019052","term":"Depression, Postpartum"}],"ancestors":[{"id":"D011644","term":"Puerperal Disorders"},{"id":"D011248","term":"Pregnancy Complications"},{"id":"D005261","term":"Female Urogenital Diseases and Pregnancy Complications"},{"id":"D000091642","term":"Urogenital Diseases"},{"id":"D003866","term":"Depressive Disorder"},{"id":"D019964","term":"Mood Disorders"},{"id":"D001523","term":"Mental Disorders"}]},"interventionBrowseModule":{"meshes":[{"id":"D004958","term":"Estradiol"},{"id":"D020280","term":"Sertraline"}],"ancestors":[{"id":"D004963","term":"Estrenes"},{"id":"D004962","term":"Estranes"},{"id":"D013256","term":"Steroids"},{"id":"D000072473","term":"Fused-Ring Compounds"},{"id":"D011083","term":"Polycyclic Compounds"},{"id":"D045166","term":"Estradiol Congeners"},{"id":"D012739","term":"Gonadal Steroid Hormones"},{"id":"D042341","term":"Gonadal Hormones"},{"id":"D006728","term":"Hormones"},{"id":"D006730","term":"Hormones, Hormone Substitutes, and Hormone Antagonists"},{"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"}]}},"hasResults":true}