Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression

NCT01407094 | Completed Phase 2 Results DMC

• 1 other identifier: STU 092010-151
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 4

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.

Conditions

Depression

Keywords

Depression, Major Depressive Disorder, Mood Disorder

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale for Depression

  The Hamilton Rating Scale for depression is a measure of depressive severity (HAM-D17; HDRS) * Scores range from 0-52 * Lower scores indicate less depressive symptomatology, and so are the more desirable.

  Week 8

Study Arms (3)

Sertraline

ACTIVE COMPARATOR

SSRI monotherapy

Drug: Sertraline

Placebo

PLACEBO COMPARATOR

Placebo control

Drug: Placebo

Bupropion

ACTIVE COMPARATOR

BupropionXL

Drug: BupropionXL

Interventions

Sertraline DRUG

50-200mg/day

Also known as: Zoloft

Sertraline

Placebo DRUG

1-4 pills per day

Placebo

BupropionXL DRUG

150-450 mg/day

Also known as: WelbutrinXL

Bupropion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (4)

Massachusetts General Hospital Boston

Boston, Massachusetts, 02114, United States

Location

University of Michigan Ann Arbor

Ann Arbor, Michigan, 48104, United States

Location

Columbia Univerisity New York City

New York, New York, 10032, United States

Location

UT Southwestern Medical Center Dallas

Dallas, Texas, 75309, United States

Location

Related Publications (21)

• Chase HW, Fournier JC, Greenberg T, Almeida JR, Stiffler R, Zevallos CR, Aslam H, Cooper C, Deckersbach T, Weyandt S, Adams P, Toups M, Carmody T, Oquendo MA, Peltier S, Fava M, McGrath PJ, Weissman M, Parsey R, McInnis MG, Kurian B, Trivedi MH, Phillips ML. Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study. PLoS One. 2015 May 11;10(5):e0126326. doi: 10.1371/journal.pone.0126326. eCollection 2015.

  PMID: 25961712 BACKGROUND

• Fournier JC, Chase HW, Greenberg T, Etkin A, Almeida JR, Stiffler R, Deckersbach T, Weyandt S, Cooper C, Toups M, Carmody T, Kurian B, Peltier S, Adams P, McInnis MG, Oquendo MA, McGrath PJ, Fava M, Weissman M, Parsey R, Trivedi MH, Phillips ML. Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression: Findings from the EMBARC Study. Biol Psychiatry Cogn Neurosci Neuroimaging. 2017 Mar;2(2):138-148. doi: 10.1016/j.bpsc.2016.11.008. Epub 2016 Dec 6.

  PMID: 28983519 BACKGROUND

• Greenberg T, Chase HW, Almeida JR, Stiffler R, Zevallos CR, Aslam HA, Deckersbach T, Weyandt S, Cooper C, Toups M, Carmody T, Kurian B, Peltier S, Adams P, McInnis MG, Oquendo MA, McGrath PJ, Fava M, Weissman M, Parsey R, Trivedi MH, Phillips ML. Moderation of the Relationship Between Reward Expectancy and Prediction Error-Related Ventral Striatal Reactivity by Anhedonia in Unmedicated Major Depressive Disorder: Findings From the EMBARC Study. Am J Psychiatry. 2015 Sep 1;172(9):881-91. doi: 10.1176/appi.ajp.2015.14050594. Epub 2015 Jul 17.

  PMID: 26183698 BACKGROUND

• Petkova E, Ogden RT, Tarpey T, Ciarleglio A, Jiang B, Su Z, Carmody T, Adams P, Kraemer HC, Grannemann BD, Oquendo MA, Parsey R, Weissman M, McGrath PJ, Fava M, Trivedi MH. Statistical Analysis Plan for Stage 1 EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care) Study. Contemp Clin Trials Commun. 2017 Jun;6:22-30. doi: 10.1016/j.conctc.2017.02.007. Epub 2017 Feb 24.

  PMID: 28670629 BACKGROUND

• Pizzagalli DA, Webb CA, Dillon DG, Tenke CE, Kayser J, Goer F, Fava M, McGrath P, Weissman M, Parsey R, Adams P, Trombello J, Cooper C, Deldin P, Oquendo MA, McInnis MG, Carmody T, Bruder G, Trivedi MH. Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Jun 1;75(6):547-554. doi: 10.1001/jamapsychiatry.2018.0252.

  PMID: 29641834 BACKGROUND

• Trivedi MH, South C, Jha MK, Rush AJ, Cao J, Kurian B, Phillips M, Pizzagalli DA, Trombello JM, Oquendo MA, Cooper C, Dillon DG, Webb C, Grannemann BD, Bruder G, McGrath PJ, Parsey R, Weissman M, Fava M. A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial. Psychother Psychosom. 2018;87(5):285-295. doi: 10.1159/000491093. Epub 2018 Aug 15.

  PMID: 30110685 BACKGROUND

• Trivedi MH, McGrath PJ, Fava M, Parsey RV, Kurian BT, Phillips ML, Oquendo MA, Bruder G, Pizzagalli D, Toups M, Cooper C, Adams P, Weyandt S, Morris DW, Grannemann BD, Ogden RT, Buckner R, McInnis M, Kraemer HC, Petkova E, Carmody TJ, Weissman MM. Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design. J Psychiatr Res. 2016 Jul;78:11-23. doi: 10.1016/j.jpsychires.2016.03.001. Epub 2016 Mar 15.

  PMID: 27038550 BACKGROUND

• Trombello JM, Pizzagalli DA, Weissman MM, Grannemann BD, Cooper CM, Greer TL, Malchow AL, Jha MK, Carmody TJ, Kurian BT, Webb CA, Dillon DG, McGrath PJ, Bruder G, Fava M, Parsey RV, McInnis MG, Adams P, Trivedi MH. Characterizing anxiety subtypes and the relationship to behavioral phenotyping in major depression: Results from the EMBARC study. J Psychiatr Res. 2018 Jul;102:207-215. doi: 10.1016/j.jpsychires.2018.04.003. Epub 2018 Apr 6.

  PMID: 29689518 BACKGROUND

• Ulke C, Tenke CE, Kayser J, Sander C, Bottger D, Wong LYX, Alvarenga JE, Fava M, McGrath PJ, Deldin PJ, Mcinnis MG, Trivedi MH, Weissman MM, Pizzagalli DA, Hegerl U, Bruder GE. Resting EEG Measures of Brain Arousal in a Multisite Study of Major Depression. Clin EEG Neurosci. 2019 Jan;50(1):3-12. doi: 10.1177/1550059418795578. Epub 2018 Sep 5.

  PMID: 30182751 BACKGROUND

• Webb CA, Trivedi MH, Cohen ZD, Dillon DG, Fournier JC, Goer F, Fava M, McGrath PJ, Weissman M, Parsey R, Adams P, Trombello JM, Cooper C, Deldin P, Oquendo MA, McInnis MG, Huys Q, Bruder G, Kurian BT, Jha M, DeRubeis RJ, Pizzagalli DA. Personalized prediction of antidepressant v. placebo response: evidence from the EMBARC study. Psychol Med. 2019 May;49(7):1118-1127. doi: 10.1017/S0033291718001708. Epub 2018 Jul 2.

  PMID: 29962359 BACKGROUND

• Chin Fatt CR, Minhajuddin A, Jha MK, Mayes T, Rush AJ, Trivedi MH. Data driven clusters derived from resting state functional connectivity: Findings from the EMBARC study. J Psychiatr Res. 2023 Feb;158:150-156. doi: 10.1016/j.jpsychires.2022.12.002. Epub 2022 Dec 27.

  PMID: 36586213 DERIVED

• Jha MK, Schatzberg A, Minhajuddin A, Chin Fatt C, Mayes TL, Trivedi MH. Cross-Sectional Associations Among Symptoms of Pain, Irritability, and Depression and How These Symptoms Relate to Social Functioning and Quality of Life: Findings From the EMBARC and STRIDE Studies and the VitalSign6 Project. J Clin Psychiatry. 2021 Apr 13;82(3):20m13740. doi: 10.4088/JCP.20m13740.

  PMID: 34000130 DERIVED

• Jha MK, Fava M, Minhajuddin A, Chin Fatt C, Mischoulon D, Cusin C, Trivedi MH. Association of anger attacks with suicidal ideation in adults with major depressive disorder: Findings from the EMBARC study. Depress Anxiety. 2021 Jan;38(1):57-66. doi: 10.1002/da.23095. Epub 2020 Oct 10.

  PMID: 33038902 DERIVED

• Chin Fatt CR, Cooper C, Jha MK, Aslan S, Grannemann B, Kurian B, Greer TL, Fava M, Weissman M, McGrath PJ, Parsey RV, Etkin A, Phillips ML, Trivedi MH. Dorsolateral Prefrontal Cortex and Subcallosal Cingulate Connectivity Show Preferential Antidepressant Response in Major Depressive Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Jan;6(1):20-28. doi: 10.1016/j.bpsc.2020.06.019. Epub 2020 Jul 8.

  PMID: 32921587 DERIVED

• Jha MK, Minhajuddin A, Chin Fatt C, Trivedi MH. Improvements in irritability with sertraline versus placebo: Findings from the EMBARC study. J Affect Disord. 2020 Oct 1;275:44-47. doi: 10.1016/j.jad.2020.06.021. Epub 2020 Jun 26.

  PMID: 32658822 DERIVED

• Rolle CE, Fonzo GA, Wu W, Toll R, Jha MK, Cooper C, Chin-Fatt C, Pizzagalli DA, Trombello JM, Deckersbach T, Fava M, Weissman MM, Trivedi MH, Etkin A. Cortical Connectivity Moderators of Antidepressant vs Placebo Treatment Response in Major Depressive Disorder: Secondary Analysis of a Randomized Clinical Trial. JAMA Psychiatry. 2020 Apr 1;77(4):397-408. doi: 10.1001/jamapsychiatry.2019.3867.

  PMID: 31895437 DERIVED

• Chin Fatt CR, Jha MK, Cooper CM, Fonzo G, South C, Grannemann B, Carmody T, Greer TL, Kurian B, Fava M, McGrath PJ, Adams P, McInnis M, Parsey RV, Weissman M, Phillips ML, Etkin A, Trivedi MH. Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression. Am J Psychiatry. 2020 Feb 1;177(2):143-154. doi: 10.1176/appi.ajp.2019.18070870. Epub 2019 Sep 20.

  PMID: 31537090 DERIVED

• Cooper CM, Chin Fatt CR, Jha M, Fonzo GA, Grannemann BD, Carmody T, Ali A, Aslan S, Almeida JRC, Deckersbach T, Fava M, Kurian BT, McGrath PJ, McInnis M, Parsey RV, Weissman M, Phillips ML, Lu H, Etkin A, Trivedi MH. Cerebral Blood Perfusion Predicts Response to Sertraline versus Placebo for Major Depressive Disorder in the EMBARC Trial. EClinicalMedicine. 2019 May 18;10:32-41. doi: 10.1016/j.eclinm.2019.04.007. eCollection 2019 Apr.

  PMID: 31193824 DERIVED

• Pillai RLI, Huang C, LaBella A, Zhang M, Yang J, Trivedi M, Weissman M, McGrath P, Fava M, Kurian B, Cooper C, McInnis M, Oquendo MA, Pizzagalli DA, Parsey RV, DeLorenzo C. Examining raphe-amygdala structural connectivity as a biological predictor of SSRI response. J Affect Disord. 2019 Sep 1;256:8-16. doi: 10.1016/j.jad.2019.05.055. Epub 2019 May 28.

  PMID: 31158720 DERIVED

• Whitton AE, Webb CA, Dillon DG, Kayser J, Rutherford A, Goer F, Fava M, McGrath P, Weissman M, Parsey R, Adams P, Trombello JM, Cooper C, Deldin P, Oquendo MA, McInnis MG, Carmody T, Bruder G, Trivedi MH, Pizzagalli DA. Pretreatment Rostral Anterior Cingulate Cortex Connectivity With Salience Network Predicts Depression Recovery: Findings From the EMBARC Randomized Clinical Trial. Biol Psychiatry. 2019 May 15;85(10):872-880. doi: 10.1016/j.biopsych.2018.12.007. Epub 2018 Dec 19.

  PMID: 30718038 DERIVED

• Liao A, Walker R, Carmody TJ, Cooper C, Shaw MA, Grannemann BD, Adams P, Bruder GE, McInnis MG, Webb CA, Dillon DG, Pizzagalli DA, Phillips ML, Kurian BT, Fava M, Parsey RV, McGrath PJ, Weissman MM, Trivedi MH. Anxiety and anhedonia in depression: Associations with neuroticism and cognitive control. J Affect Disord. 2019 Feb 15;245:1070-1078. doi: 10.1016/j.jad.2018.11.072. Epub 2018 Nov 14.

  PMID: 30699849 DERIVED

MeSH Terms

Conditions

Depression; Depressive Disorder, Major; Mood Disorders

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Madhukar H. Trivedi
• Organization: University of Texas Southwestern Medical Center

madhukar.trivedi@UTSouthwestern.edu

214-648-0188

Study Officials

• Madhukar H Trivedi, M.D.

  University of Texas 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients were entered into Stage 1, treated with sertraline (Treatment A) or placebo (Treatment B), and used for the primary analysis which included the identification of potential mediators and moderators of response for these two treatments. In stage two, responders to Treatment A remained on sertraline, and non-responders were switched to bupropion (Treatment C). Responders to Treatment B remained on placebo, and non-responders were switched to sertraline (Treatment D).

Study Record Dates

• First Submitted: July 25, 2011
• First Posted: August 1, 2011
• Study Start: July 29, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: December 26, 2018
• Results First Posted: December 26, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share

Locations

US (4)