Back to resultsBupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
Primary Purpose
Major Depression
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Bupropion XL
Escitalopram
Sponsored by
About this trial
This is an interventional treatment trial for Major Depression focused on measuring Inflammation
Eligibility 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
Sites / Locations
- Emory ClinicRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Bupropion
Escitalopram
Arm Description
Participants randomized to take bupropion for 8 weeks.
Participants randomized to take escitalopram for 8 weeks.
Outcomes
Primary Outcome Measures
Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC)
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
Change in Effort-Expenditure for Rewards Task (EEfRT) Score
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.
Change in Snaith-Hamilton Pleasure Scale (SHAPS-C) Score
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.
Change in Motivation and Pleasure Scale-Self-Report (MAP-SR) Score
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.
Change in Inventory of Depressive Symptomatology - Self-Report (IDS-SR)
The IDS-SR is a 30-item self-reported measurement of depression severity. Responses are given on a 4-point scale where 0 = no problems and 3 = severe problems. Total scores are based on 28 items and range from 0 to 84 with higher scores indicating more severe symptoms of depression.
Full Information
NCT ID
NCT04352101
First Posted
April 16, 2020
Last Updated
January 23, 2023
Sponsor
Emory University
Collaborators
National Institute of Mental Health (NIMH)
1. Study Identification
Unique Protocol Identification Number
NCT04352101
Brief Title
Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
Official Title
Effects of Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits in Patients With Major Depression and Increased Inflammation and Anhedonia
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 23, 2020 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
National Institute of Mental Health (NIMH)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depression
Keywords
Inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Bupropion
Arm Type
Experimental
Arm Description
Participants randomized to take bupropion for 8 weeks.
Arm Title
Escitalopram
Arm Type
Active Comparator
Arm Description
Participants randomized to take escitalopram for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Bupropion XL
Other Intervention Name(s)
Wellbutrin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Escitalopram
Other Intervention Name(s)
Lexapro
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in Targeted Ventromedial Prefrontal Cortex-Ventral Striatal (vmPFC-VS) Functional Connectivity (FC)
Description
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.
Time Frame
Baseline, Week 4, Week 8
Secondary Outcome Measure Information:
Title
Change in Effort-Expenditure for Rewards Task (EEfRT) Score
Description
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.
Time Frame
Baseline, Week 2, Week 4, Week 6, Week 8
Title
Change in Snaith-Hamilton Pleasure Scale (SHAPS-C) Score
Description
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.
Time Frame
Baseline, Week 2, Week 4, Week 6, Week 8
Title
Change in Motivation and Pleasure Scale-Self-Report (MAP-SR) Score
Description
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.
Time Frame
Baseline, Week 2, Week 4, Week 6, Week 8
Title
Change in Inventory of Depressive Symptomatology - Self-Report (IDS-SR)
Description
The IDS-SR is a 30-item self-reported measurement of depression severity. Responses are given on a 4-point scale where 0 = no problems and 3 = severe problems. Total scores are based on 28 items and range from 0 to 84 with higher scores indicating more severe symptoms of depression.
Time Frame
Baseline, Week 2, Week 4, Week 6, Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrew Miller, MD
Phone
404-727-8260
Email
amill02@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Miller, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
Data will become available two years after the publication of the main findings from the study.
IPD Sharing 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.
Learn more about this trial
Bupropion Versus Escitalopram on Reward Circuitry and Motivational Deficits
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