Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04352101
Recruitment Status : Recruiting
First Posted : April 20, 2020
Last Update Posted : January 11, 2021
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Andrew H Miller, Emory University

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.

Condition or disease Intervention/treatment Phase
Major Depression Drug: Bupropion XL Drug: Escitalopram Phase 4

Detailed Description:

The goal of the proposed research is to determine the mechanism of action of an antidepressant of known efficacy (bupropion) and to tie this mechanism of action to a biomarker of inflammation in support of precision medicine for the treatment of major depression (MD). MD is a devastating disease affecting approximately 10% of US adults and being the leading cause of disability worldwide. Despite availability of several classes of antidepressant medications, initial treatment response is low (around 30%), and approximately 1/3 of depressed patients are non-responsive to conventional antidepressant therapies. Although extensive reviews of the literature suggest that available antidepressant medications are equally effective, recent studies suggest that there may be differential responsiveness to conventional antidepressants among subgroups of depressed patients. One subgroup of depressed patients who may exhibit differential antidepressant responsiveness are those with increased markers of inflammation. Data from previous studies support the notion that differential responsiveness to conventional antidepressants exists and may be revealed by pretreatment levels of inflammation as indexed by the inflammatory biomarker C-reactive protein (CRP).

This study proposes to use a mechanistic clinical trial design with drugs of known efficacy to take the first step toward establishing whether antidepressants that target dopamine (e.g. bupropion) might be a better choice for depressed patients with increased inflammation and anhedonia than an selective serotonin reuptake inhibitor (SSRI). Accordingly, 50 depressed patients with a CRP>2mg/L and increased anhedonia will be randomized to 8 weeks of bupropion or escitalopram in order to analyze data from 40 patients (accounting for drop outs). All depressed patients will undergo functional magnetic resonance imaging (fMRI) to examine functional connectivity in reward-related circuits at baseline and 4 and 8 weeks along with objective and clinical assessments of Research Domain Criteria (RDoC) positive (motivational) valence constructs at baseline and 2, 4, 6 and 8 weeks.

The researchers hypothesize that patients who receive bupropion versus escitalopram will exhibit increased functional connectivity between ventral striatum and ventromedial prefrontal cortex in association with decreased motivational deficits and anhedonia.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits in Patients With Major Depression and Increased Inflammation and Anhedonia
Actual Study Start Date : September 23, 2020
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022


Arm Intervention/treatment
Experimental: Bupropion
Participants randomized to take bupropion for 8 weeks.
Drug: Bupropion XL
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.
Other Name: Wellbutrin

Active Comparator: Escitalopram
Participants randomized to take escitalopram for 8 weeks.
Drug: Escitalopram
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.
Other Name: Lexapro




Primary Outcome Measures :
  1. Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC) [ Time Frame: Baseline, Week 4, Week 8 ]
    Targeted FC will be 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. Z-scores will be extracted and the change in mean FC values compared to baseline will be calculated.


Secondary Outcome Measures :
  1. Change in Effort-Expenditure for Rewards Task (EEfRT) Score [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]
    The EEfRT task is a multi-trial game in which participants are given an opportunity to choose different task difficulty levels to obtain monetary rewards (easy tasks have low rewards while hard tasks have higher rewards). The task is 20 min, and first 50 trials are analyzed. Each trial has a high, medium, or low probability of success, and this information is given to the participant when they are deciding between easy and hard tasks. The proportion of hard-task choices across each level of probability is calculated. Lower proportions of hard task choices indicate decreased motivation.

  2. Change in Snaith-Hamilton Pleasure Scale (SHAPS-C) Score [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]
    The SHAPS-C is a 14-item clinician-administered scale assessing the amount of pleasure during common daily activities that the participant has experienced in the past week. Responses are given on a scale of 1 to 4 where 1 = lots of pleasure and 4 = no pleasure. Total scores range from 14 to 56 with lower scores indicating greater enjoyment of activities.

  3. Change in Motivation and Pleasure Scale-Self-Report (MAP-SR) Score [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]
    The MAP-SR is an 18-item self-report inventory that has been validated in psychiatric populations and is designed to disentangle motivational and consummatory components of everyday activities over a 24-hr period. Responses are given on a 5-point scale where 0 = no pleasure or motivation and 4 = extreme pleasure or motivation. Total scores range from 0 to 72 and higher scores indicate greater motivation and pleasure during everyday activities.

  4. Change in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) [ Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8 ]
    The 16 item QIDS-SR is a self-reported measurement of depression severity. Responses are given on a 4-point scale where 0 = no problems and 3 = severe problems. Respondents provide answers for 14 of the 16 items (depending on their symptoms). Total scores range from 0 to 42 with higher scores indicating more severe symptoms of depression.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   25 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 (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
  • IDS-SR anhedonia subscale score ≥5

Exclusion Criteria:

  • 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.
  • sexually active participants are required to use medically approved birth control methods as defined in the Birth Control Method Form for the duration of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04352101


Contacts
Layout table for location contacts
Contact: Bobbi Woolwine, LCSW 404-712-9620 bwoolwi@emory.edu

Locations
Layout table for location information
United States, Georgia
Emory Clinic Recruiting
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Emory University
National Institute of Mental Health (NIMH)
Investigators
Layout table for investigator information
Principal Investigator: Andrew Miller, MD Emory University
Layout table for additonal information
Responsible Party: Andrew H Miller, Professor, Emory University
ClinicalTrials.gov Identifier: NCT04352101    
Other Study ID Numbers: IRB00117673
1R21MH121891 ( U.S. NIH Grant/Contract )
First Posted: April 20, 2020    Key Record Dates
Last Update Posted: January 11, 2021
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The database generated by the study will be made available to the broader research community upon request accompanied by documentation of local institutional review board (IRB) approval. Investigators will provide relevant protocols and published phenotypic and clinical data upon request.
Supporting Materials: 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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andrew H Miller, Emory University:
Inflammation
Additional relevant MeSH terms:
Layout table for MeSH terms
Depression
Depressive Disorder, Major
Behavioral Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Citalopram
Bupropion
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Dopamine Agents
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors