Ignite Creation Date:
2025-12-25 @ 1:43 AM
Ignite Modification Date:
2025-12-27 @ 11:49 PM
Study NCT ID:
NCT01407094
Status:
COMPLETED
Last Update Posted:
2018-12-26
First Post:
2011-07-25
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression
Sponsor:
University of Texas Southwestern Medical Center
Organization:
Study Overview
Official Title:
Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) for Depression
Status:
COMPLETED
Status Verified Date:
2018-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EMBARC
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.
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 a 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 the 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.
Primary Outcomes:
\- 17-item Hamilton Rating Scale for Depression (HRSD17)
Secondary Outcomes:
\- the Frequency, Intensity, and Burden Side Effects Rating (FIBSER)
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 the 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.
Primary Outcomes:
\- 17-item Hamilton Rating Scale for Depression (HRSD17)
Secondary Outcomes:
\- the Frequency, Intensity, and Burden Side Effects Rating (FIBSER)
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: