Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Texas Southwestern Medical Center
Sponsor:
Information provided by (Responsible Party):
Madhukar H. Trivedi, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01407094
First received: July 25, 2011
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Depression
Drug: Sertraline
Drug: Placebo
Drug: BupropionXL
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) for Depression

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Hamilton Rating Scale for Depression [ Time Frame: Week 16 ] [ Designated as safety issue: Yes ]
    Measure of depressive severity


Estimated Enrollment: 400
Study Start Date: July 2011
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sertraline
SSRI monotherapy
Drug: Sertraline
50-200mg/day
Other Name: Zoloft
Placebo Comparator: Placebo
Placebo control
Drug: Placebo
1-4 pills per day
Other Name: Placebo
Active Comparator: Bupropion
BupropionXL
Drug: BupropionXL
150-450 mg/day
Other Name: WelbutrinXL

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adults, age 18-65
  • Written informed consent obtained
  • Outpatients with a current primary diagnosis of nonpsychotic recurrent or chronic MDD per the SCID-I
  • QIDS-SR score of ≥ 14 at Screening Visit and Randomization (Baseline) Visit
  • No failed antidepressant trials of adequate dose and duration, as defined by the MGH-ATRQ, in the current episode
  • Agrees to, and is eligible for, all biomarkers procedures (EEG/psychological testing, MRI, and blood draws)

Exclusion Criteria:

  • History of inadequate response (to trials at adequate dose for adequate duration) or poor tolerability to sertraline (SERT) or bupropion (BUP)
  • Pregnant or breastfeeding
  • Plan to become pregnant over the ensuing 12 months following study entry or are sexually active and not using adequate contraception
  • History (lifetime) of psychotic depression, schizophrenia, bipolar (I, II, or NOS) disorder, schizoaffective disorder, or other Axis I psychotic disorder
  • Current primary anxiety disorder diagnosis
  • Meeting DSM-IV criteria for substance abuse in the last 2 months or substance dependence in the last 6 months (except for nicotine)
  • Require immediate hospitalization for psychiatric disorder
  • Have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy < 6 months after study entry)
  • Require medications for their GMCs that contraindicate any study medication
  • Have epilepsy or other conditions requiring an anticonvulsant
  • Receiving or have received during the index episode vagus nerve stimulation, ECT, or rTMS, or other somatic antidepressant treatments
  • Currently taking any of the following exclusionary medications: antipsychotic medications, anticonvulsant medications, mood stabilizers, central nervous system stimulants, daily use of benzodiazepines or hypnotics, or antidepressant medication used for the treatment of depression or other purposes such as smoking cessation, since these agents may interfere with the testing of the major hypotheses under study. Nonexcluded concomitant medications are acceptable as long as their clinician determines that antidepressant treatment is safe and appropriate.
  • Significant liver disease that would contraindicate any study medication
  • Taking thyroid medication for hypothyroidism may be included only if they have been stable on the thyroid medication for 3 months
  • Using agents that are potential augmenting agents (e.g., T3 in the absence of thyroid disease, SAMe, St. John's Wort, lithium, buspirone, Omega 3 fatty acids)
  • Therapy that is depression specific, such as CBT or Interpersonal Psychotherapy of Depression (IPT) is not allowed during participation (participants can participate if they are receiving psychotherapy that is not targeting the symptoms of depression, such as supportive therapy, marital therapy).
  • Subjects must be fluent in English and have the capacity to understand the nature of the study and sign the written informed consent since non-English speaking personnel are not available for this study, and the research instruments are not yet translated and validated in other languages.
  • Currently actively suicidal or considered a high suicide risk
  • Are currently enrolled in another study, and participation in that study contraindicates participation in the EMBARC study.
  • Any reason not listed herein yet, determined by the site PI, medical personnel, or designee that constitutes good clinical practice and that would in the opinion of the site PI, medical personnel, or designee make participation in the study hazardous.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407094

Contacts
Contact: Sarah Weyandt, Ph.D. 214-648-4629 sarah.weyandt@utsouthwestern.edu
Contact: David W Morris, Ph.D. 214-648-0162 davidw.morros@utsouthwestern.edu

Locations
United States, Massachusetts
Massachusetts General Hospital Boston Recruiting
Boston, Massachusetts, United States, 02114
Contact: Angela Pisoni    617-726-0517    apisoni@partners.org   
Contact: Ilana Huz    617-724-3520    ihuz@partners.org   
United States, Michigan
University of Michigan Ann Arbor Recruiting
Ann Arbor, Michigan, United States, 48104
Contact: Christine Brucksch    877-864-3637    UM-MDDResearch@umich.edu   
United States, New York
Columbia Univerisity New York City Recruiting
New York City, New York, United States, 10032
Contact: Vito Agosti    212-543-5605    agostiv@nyspi.columbia.edu   
Contact: Donna O'Shea    212-543-5671    osheado@nyspi.columbia.edu   
United States, Texas
UT Southwestern Medical Center Dallas Recruiting
Dallas, Texas, United States, 75309
Contact: Erin Hyken    214-648-0157    erin.hyken@utsouthwestern.edu   
Contact: Aasia Ali    214-648-0829    aasia.ali@utsouthwestern.edu   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Madhukar H Trivedi, M.D. UT Southwestern Medical Center
Principal Investigator: Patrick J McGrath, M.D. Columbia University
Principal Investigator: Myrna Weissman, Ph.D. Columbia University
Principal Investigator: Ramin Parsey, M.D. Columbia University
Principal Investigator: Maurizio Fava, M.D. Massachusetts General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Madhukar H. Trivedi, Principal Investigator, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01407094     History of Changes
Other Study ID Numbers: STU 092010-151
Study First Received: July 25, 2011
Last Updated: December 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:
Depression, Major Depressive Disorder, Mood Disorder

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mental Disorders
Mood Disorders
Antidepressive Agents
Sertraline
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014