Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC)
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First Received Date ICMJE | July 25, 2011 | ||||||||||||||||||||
Last Updated Date | August 21, 2012 | ||||||||||||||||||||
Start Date ICMJE | July 2011 | ||||||||||||||||||||
Estimated Primary Completion Date | June 2014 (final data collection date for primary outcome measure) | ||||||||||||||||||||
Current Primary Outcome Measures ICMJE |
Hamilton Rating Scale for Depression [ Time Frame: Week 16 ] [ Designated as safety issue: Yes ] Measure of depressive severity |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||
Change History | Complete list of historical versions of study NCT01407094 on ClinicalTrials.gov Archive Site | ||||||||||||||||||||
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Descriptive Information | |||||||||||||||||||||
Brief Title ICMJE | Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression | ||||||||||||||||||||
Official Title ICMJE | Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) for Depression | ||||||||||||||||||||
Brief Summary | This study will examine multiple carefully selected clinical and biological markers, using both existing state-of-the-art technologies as well as pioneering, innovative approaches. The study is designed to identify moderators and mediators of treatment response for depression in order to specify a biosignature of treatment response for depression. Evaluation of the usefulness of these markers in a carefully conducted clinical trial comparing an antidepressant to placebo will assist in developing a Depression Treatment Response Index (DTRI) to help clinicians match treatments to patients with MDD, resulting in timely selection of treatments best suited for individual patients and thus approaching personalized treatment. The resulting index provides a truly novel means of synthesizing the contribution of key clinical and biological parameters in an easy to use tool for clinical care. |
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Detailed Description | The current study is designed to identify biomarkers for the prediction of differential treatment outcomes between the SSRI antidepressant sertraline (SERT) and placebo (PBO) in a randomized trial for patients with MDD. In addition, a second stage will collect data to explore moderators and mediators of treatment outcomes between pharmacologically distinct active treatment arms: sertraline (SERT), a serotonergic antidepressant or bupropion (BUP), a nonserotonergic antidepressant. To reduce biologic heterogeneity, we will only enroll patients with early onset of DSM IV MDD (before age 30) because these criteria in probands have been shown to be associated with increased familial loading in families. Patients will also have recurrent MDD with 2 or more recurrences (including current episode). Additionally, patients will be required to have a current symptom severity score of 14 or more on the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR), both at study screening and at the randomization (baseline) visit. In the first stage, patients will receive an 8−week course of treatment in one of the two study arms. As part of the Sequential Multiple Assignment Randomized Trial (SMART) design patients that have not achieved response at the end of 8 weeks to their stage one treatment, defined by < 50% improvement on the Clinical Global Improvement scale (CGI), will be switched to Stage 2 treatment (8 weeks). Patients who have achieved satisfactory response (>= 50% improvement on the CGI) will be continued on treatment for an additional 8 weeks. Specific Aims Moderator Aims (Aim 1): To identify baseline clinical, neuroimaging, neurophysiological, and behavioral moderators of differential treatment outcome (mean symptom change and tolerability) for sertraline (SERT, a serotonergic antidepressant) versus placebo (PBO) for the treatment of MDD. Symptom change will be measured using mean change from baseline in the 17-item Hamilton Rating Scale for Depression (HRSD17). Tolerability will be measured using the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) and the Treatment Emergent Symptom Scale (TESS). Mediator Aims (Aim 2): To identify early phase (week 1) changes in neuroimaging, neurophysiological, and behavioral tasks as mediators of differential treatment outcomes (symptom change, tolerability) to SERT and PBO. Main Treatment Effects Aim (Aim 3): To compare the 8-week outcomes of SERT vs. PBO using mixed model regression analysis to maximize power to discriminate treatment efficacy differences. |
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Study Type ICMJE | Interventional | ||||||||||||||||||||
Study Phase | Phase 4 | ||||||||||||||||||||
Study Design ICMJE | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Depression | ||||||||||||||||||||
Intervention ICMJE |
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Study Arm (s) |
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Publications * | |||||||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||||||||
Recruitment Status ICMJE | Recruiting | ||||||||||||||||||||
Estimated Enrollment ICMJE | 400 | ||||||||||||||||||||
Estimated Completion Date | June 2014 | ||||||||||||||||||||
Estimated Primary Completion Date | June 2014 (final data collection date for primary outcome measure) | ||||||||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||||||||||||||||||
Ages | 18 Years to 65 Years | ||||||||||||||||||||
Accepts Healthy Volunteers | Yes | ||||||||||||||||||||
Contacts ICMJE |
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Location Countries ICMJE | United States | ||||||||||||||||||||
Administrative Information | |||||||||||||||||||||
NCT Number ICMJE | NCT01407094 | ||||||||||||||||||||
Other Study ID Numbers ICMJE | STU 092010-151 | ||||||||||||||||||||
Has Data Monitoring Committee | Yes | ||||||||||||||||||||
Responsible Party | Madhukar H. Trivedi, University of Texas Southwestern Medical Center | ||||||||||||||||||||
Study Sponsor ICMJE | University of Texas Southwestern Medical Center | ||||||||||||||||||||
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Investigators ICMJE |
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Information Provided By | University of Texas Southwestern Medical Center | ||||||||||||||||||||
Verification Date | August 2012 | ||||||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |