Neurobiological Underpinnings of Placebo Response in Depression

NCT02562430 | Completed Phase 4 Results DMC

• 1 other identifier: 2014P000889
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

In summary, the proposed research is novel with respect to design, technology, and its multi-level integration probing psychological and neurobiological constructs assumed to be crucially implicated in placebo response and has significant clinical and research implications for the future. Specifically, the future implications include: 1) identification of biomarkers and biosignatures of placebo responders, 2) new possibilities to understanding and manipulating the system, 3) possibly decreasing or eliminating a major confounder in clinical trials and drug development, and 4) refining treatments with novel drugs that decrease (in clinical trial) or increase (in clinical practice) the placebo response.

Conditions

Depression

Keywords

Placebo response

Outcome Measures

Primary Outcomes (1)

• HAM-D 32

  The HAM-D-32 (Hamilton Depression Rating Scale) scores can range between 0 and 124, with higher scores indicating more severe depression. Total score was reported here.

  8 weeks

Study Arms (2)

Active Treatment

EXPERIMENTAL

12.5 % will be randomized to Welbutrin XL in phase 1 of the study.

Drug: Welbutrin XL

Placebo Group

ACTIVE COMPARATOR

87.5% will be randomized to receive placebo in phase 1 of the study.

Drug: Placebo

Interventions

Welbutrin XL DRUG

12.5% of participants will receive Welbutrin XL in phase 1 of the study.

Also known as: Buproprion XL

Active Treatment

Placebo DRUG

87.5% of subjects will be randomized to placebo in phase 1 of the study.

Also known as: Sugar pill

Placebo Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In addition to fulfilling the diagnostic criteria for MDD, the following conditions must be met for patient eligibility:
• Written informed consent
• Men or women aged 18 to 60 years old
• A score of 16 or greater on the Hamilton Depression Rating Scale -32 items (HAM-D- 32)
• Continuing to meet criteria for current MDD at baseline and Clinical Global Impression Improvement (CGI) scores ≤ 3 (i.e. minimally improved or less) from the screen to the baseline visit
• Only one failed one prior antidepressant in the current episode or are currently taking an antidepressant as defined by the MGH-ATRQ, in the current episode and are willing to take bupropion or placebo as augmentation, since we are using subjects as their own controls and we are comparing changes within subjects. Subjects with secondary anxiety disorders, like panic, GAD or simple phobia will be allowed, in order to make the population studied more representative of the general population of MDD.

You may not qualify if:

• Pregnant women or women of child bearing potential not using a medically accepted means of contraception.
• Serious suicide or homicide risk.
• Unstable medical illnesses, any history of seizure disorder.
• The following DSM-IV diagnoses: a) organic mental disorders; b) substance use disorders, including alcohol abuse, within the last year; c) psychotic disorders; d) bipolar disorder; e) acute bereavement; f) severe borderline or antisocial personality disorder; g) history of eating disorder unless if in remission for ≥5 years prior to screening and presenting no current electrolyte abnormalities; h) current primary diagnoses of panic disorder, social phobia, PTSD, GAD, or OCD; i) mood congruent or mood incongruent psychotic features.
• History of hepatic impairment or congestive heart failure.
• Any history of abuse of stimulants or opiates.
• Any investigational psychotropic drug within the last year.
• Subjects who have not responded to two or more antidepressant trials of adequate doses (e.g., fluoxetine 40 mg/day or higher) and duration (e.g., ≥6 weeks) over the past five years according to the ATRQ.
• History of inadequate response/poor tolerability to bupropion.
• Subjects with medical contraindications to bupropion (e.g., history of seizures, uncontrolled electrolyte imbalance due to eating disorders, etc.) unless stable for 8 weeks prior to screening and there will be no changes during participation in the study.
• Any unstable concomitant form of psychotherapy (depression-focused). Concomitant psychotherapy would be allowed if the frequency and the modality have been stable for the 8 weeks prior to screening and there will be no changes during the participation to the study
• Receiving or have received during the index episode VNS, ECT or rTMS.
• Color-blindness for blue or green (see fMRI task).

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Depression Clinical and Research Program at Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Depression

Interventions

Sugars

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Carbohydrates

Results Point of Contact

• Title: Cristina Cusin
• Organization: Massachusetts General Hospital

ccusin@mgh.harvard.edu

617-724-5510

Study Officials

• Cristina Cusin, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Psychiatrist

Study Record Dates

• First Submitted: September 25, 2015
• First Posted: September 29, 2015
• Study Start: August 1, 2016
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2022
• Last Updated: May 14, 2026
• Results First Posted: May 14, 2026

Record last verified: 2025-12

Locations

US (1)