Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits

NCT04352101 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: IRB001176731R21MH121891
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to determine whether bupropion (vs escitalopram) increases functional connectivity (FC) within reward-related neurocircuits and decreases motivational deficits in depressed patients with increased inflammation and anhedonia. Participants will be randomized to take bupropion extended release (XL) or escitalopram for 8 weeks.

Conditions

Major Depression

Keywords

Inflammation

Outcome Measures

Primary Outcomes (1)

• Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC)

  Targeted FC is calculated as the degree of correlation in activity between a 3mm3 radius sphere in VS and the vmPFC cluster identified as being reward-sensitive in neuroimaging meta-analyses and as used to define vmPFC in previous work. Subject-level correlations for degree of vmPFC-VS FC is Fisher's Z transformed {Z(R)=0.5ln\[(1+R)/(1-R)\]}, a standard method for calculating fMRI functional connectivity, whereby greater Z-scores reflected stronger correlated functional magnetic resonance imaging (fMRI) activity (i.e., higher VS-vmPFC connectivity). For each study timepoint, Z-scores will be extracted and the change in mean FC values compared to baseline will be calculated. The central value is 0, and the standard deviation depends on the sample variance. Increasing values indicate increasing connectivity between the indicated brain regions (VS and vmPFC). There are no relevant thresholds, and there is no direct interpretation of results in terms of clinical improvement.

  Baseline, Week 4, Week 8

Secondary Outcomes (4)

• Proportion of Hard-Task Choices During the Effort-Expenditure for Rewards Task (EEfRT)

  Baseline, Week 2, Week 4, Week 8

• Snaith-Hamilton Pleasure Scale (SHAPS-C) Score

  Baseline, Week 2, Week 4, Week 6, Week 8

• Motivation and Pleasure Scale-Self-Report (MAP-SR) Score

  Baseline, Week 2, Week 4, Week 6, Week 8

• Inventory of Depressive Symptomatology - Self-Report (IDS-SR)

  Baseline, Week 2, Week 4, Week 6, Week 8

Study Arms (2)

Bupropion

EXPERIMENTAL

Participants randomized to take bupropion for 8 weeks.

Drug: Bupropion XL

Escitalopram

ACTIVE COMPARATOR

Participants randomized to take escitalopram for 8 weeks.

Drug: Escitalopram

Interventions

Bupropion XL DRUG

Participants will take 150 milligrams per day (mg/d) of bupropion XL for two weeks, then the dose will be increased to 300mg/d, as tolerated, for the remaining 6 weeks of the study.

Also known as: Wellbutrin

Bupropion

Escitalopram DRUG

Participants will take 10mg/d of escitalopram for two weeks, then the dose will be increased to 20mg/d, as tolerated, for the remaining 6 weeks of the study.

Also known as: Lexapro

Escitalopram

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• willing and able to give written informed consent
• a primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders (DSM-V) MD, current as diagnosed by the Structured Clinical Interview for DSM-V Axis I Disorders (SCID-V)
• score of ≥16 on the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)
• off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine); concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments
• CRP\>2mg/L
• Inventory of Depressive Symptomatology (IDS-SR) anhedonia subscale score ≥5

You may not qualify if:

• history of any autoimmune disorder
• history of hepatitis B or C infection or human immunodeficiency virus infection
• history of any type of cancer requiring treatment with more than minor surgery
• unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing)
• history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry (as determined by SCID)
• an active eating disorder or antisocial personality disorder
• a history of a cognitive disorder or ≤28 on the Mini-Mental State Exam unless otherwise approved by the PI
• pregnancy or lactation
• chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications
• use of NSAIDS or oral glucocorticoids at any time during the study
• any contraindication for MRI scanning
• failure of more than 2 antidepressant trials in the current episode
• Intolerance of bupropion or escitalopram
• BMI \>40 (to exclude severe obesity)
• due to the high co-morbidity between anxiety disorders and depression, the study team plans to include patients with anxiety-related disorders excluding obsessive-compulsive disorder (OCD) if depression is the primary diagnosis. Patients with stable medical conditions and on medications for those conditions will not be excluded. Concomitant administration of up to 2 mg of clonazepam or its equivalent per day will be allowed, but not within 12 hours of study assessments.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Inflammation

Interventions

Bupropion; Escitalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Propylamines; Amines; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Andrew H. Miller, MD
• Organization: Emory University

amill02@emory.edu

404-727-8260

Study Officials

• Andrew Miller, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 20, 2020
• Study Start: September 23, 2020
• Primary Completion: July 25, 2022
• Study Completion: July 25, 2022
• Last Updated: December 29, 2023
• Results First Posted: December 29, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will become available two years after the publication of the main findings from the study.
• Access Criteria: Material transfers will be made with no more restrictive terms than in the Simple Letter Agreement (SLA) or the Uniform Biological Materials Transfer Agreement (UBMTA) and without reach through requirements. Should any intellectual property arise which requires a patent, the researchers will ensure that the technology (materials and data) remains widely available to the research community in accordance with University policies and the NIH Principles and Guidelines document. A variety of models for data sharing may be adopted, including both central databases and peer-to-peer solutions. Appropriate de-identification techniques should allow sharing of human data, while maintaining appropriate privacy required by both HIPAA and the Common Rule. In addition, informed consent documents should provide sufficient detail about the intent to archive, share and re-analyze data (and samples). Decisions about sharing materials will be made by the study PIs.

Locations

US (1)