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Effects of Bupropion in Depression

Primary Purpose

Depression

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Bupropion
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Depression focused on measuring Anhedonia, Dopamine, Bupropion, fMRI, emotional processing, reward

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Participants must have signed an informed consent document indicating they understand the purpose of the study and the procedures required for the study and are willing to participate by complying with the study procedures and restrictions
  • Participants will be male or female and aged between 18 and 50
  • Participants will have a Body Mass Index (BMI) 18 to 36 kg/m2 (inclusive) at the Screening Visit.
  • The MDD participants must satisfy a diagnosis of MDD as determined by structured clinical interview for DSM-V (SCID) conducted by a psychiatrist. The MDD subtypes characterized under DSM-V also will be determined for use during post hoc tests aimed at characterizing further the heterogeneity extant within the MDD population.
  • Participants must be sufficiently fluent in English to complete the emotional and reward tasks.

Exclusion Criteria:

  • Current use of psychotropic medication or electroconvulsive therapy (within three weeks of the baseline assessments) or psychological treatment (within 3 months of the baseline assessments)
  • They are left handed (the site of brain activations vary depending on handedness)
  • They are not fluent in English
  • History of stimulant abuse (lifetime; e.g., amphetamine, cocaine), or of alcohol abuse within one year or of alcohol dependence within the lifetime.
  • History of, or current medical conditions which in the opinion of the investigator may interfere with the scientific assessments or safety of the participant, including brain injury, epilepsy/seizures, severe hepatic cirrhosis and CNS tumour.
  • Clinically significant abnormal values for liver function tests, clinical chemistry, urine drug screen, blood pressure measurement and ECG. It is expected that laboratory values will generally be within the normal range for the laboratory. NB clinical significance will be determined by a qualified study medic who will review the results and the participant.
  • Current pregnancy or breastfeeding
  • Smoker > 10 cigarettes per day or similar levels of tobacco consumption in other forms. History of smoking within 8 weeks of becoming abstinent.
  • Any contraindication to MRI scanning, for example any metal implants in the body that include ferromagnetic objects in their bodies (e.g., metal implants, vessel clips, shrapnel injuries) or with implanted devices which may be damaged by the magnet (e.g., heart pacemakers).
  • Participation in a psychological or medical study involving the use of medication within the last 3 months. Previous participation in any study involving the emotional test battery.
  • Has clinically significant risk of suicidal behaviour.
  • Medical conditions that may alter the hemodynamic parameters underlying the BOLD signal (e.g., inadequately treated hypertension, diabetes mellitus).

The following exclusion criteria apply specifically to the participants in the MDD group:

  • Any known allergy, hypersensitivity or intolerance to bupropion or its excipients.
  • Has any contraindication to the use of bupropion.
  • Any medical contraindication, for example conditions or treatments that may alter the absorption of bupropion such as surgical treatments involving the gut.
  • History of or current Axis 1 DSM-V psychiatric disorder (except depression or anxiety disorders such as specific phobia or social anxiety disorder for the MDD group and drug abuse subject to the criteria outlined below).The presence of co-morbid anxiety disorders will be recorded for potential use in post hoc exploratory analyses of the influence of such conditions on the outcome measures

The following criteria apply specifically to participants in the healthy control group:

• History of or current Axis 1 DSM-V psychiatric disorder

Sites / Locations

  • University of Oxford

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Depressed patient given bupropion

Control pts given no intervention

Arm Description

All depressed patients will be given open label bupropion

Control participants will be assessed at the same time points as the depressed group, but will be given no drug

Outcomes

Primary Outcome Measures

Change in haemodynamic (i.e. BOLD signal) response
fMRI data collected during a reward and emotional coding task

Secondary Outcome Measures

Change in questionnaire measures of subject mood and anhedonia
Standardised questionnaire measures of depressive symptoms and anhedonia.
Change in accuracy and reaction time
Behavioral responses during computer based tasks measures cognition

Full Information

First Posted
March 24, 2014
Last Updated
May 10, 2016
Sponsor
University of Oxford
Collaborators
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02104128
Brief Title
Effects of Bupropion in Depression
Official Title
Effects of Bupropion in Depression
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Janssen Research & Development, LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study will investigate the role of dopaminergic neural systems in the symptoms and treatment of depression. 40 patients who meet DSM-IV criteria for a diagnosis of depression will be compared to a matched sample of healthy controls. The depressed group will receive open label treatment with Bupropion MR (150mg bd) for 6 weeks. The control group will receive no treatment. All participants will be assessed before treatment, after 2 weeks treatment and at 6 weeks treatment. The outcomes assessed will be 1) fMRI estimates of neural response to reward to emotionally valenced stimuli (1st and 2nd assessments), 2) computer based measures of emotional processing (all assessments) and 3) standardised questionnaire measures of depressive symptoms (all assessments). The primary study hypothesis is that altering central dopamine using Bupropion will lead to altered neural responses to rewarding stimuli in the depressed patients (i.e. comparing fMRI outcomes between assessment visits 1 and 2). A secondary hypothesis is that this neural change will predict subsequent symptom response to the bupropion (i.e. comparing symptom scores between assessment visits 1 and 3), Lastly, the study will test the hypothesis that baseline differences in reward circuitry will be particularly associated with symptoms of anhedonia (the inability to experience pleasure).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression
Keywords
Anhedonia, Dopamine, Bupropion, fMRI, emotional processing, reward

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Depressed patient given bupropion
Arm Type
Experimental
Arm Description
All depressed patients will be given open label bupropion
Arm Title
Control pts given no intervention
Arm Type
No Intervention
Arm Description
Control participants will be assessed at the same time points as the depressed group, but will be given no drug
Intervention Type
Drug
Intervention Name(s)
Bupropion
Other Intervention Name(s)
Zyban
Intervention Description
Bupropion MR will be given open label to all participants in the depression group. Participants will receive 150mg od for one week. The dose will then be increased to 150mg bd for the following 5 weeks. Participants in the control group will recieve no drug. Note that the study is not assessing the safety or efficacy of buprion-- it is using bupropion to assess the neural effects of altering central dopaminergic function in depressed patients.
Primary Outcome Measure Information:
Title
Change in haemodynamic (i.e. BOLD signal) response
Description
fMRI data collected during a reward and emotional coding task
Time Frame
Baseline and 2 weeks
Secondary Outcome Measure Information:
Title
Change in questionnaire measures of subject mood and anhedonia
Description
Standardised questionnaire measures of depressive symptoms and anhedonia.
Time Frame
baseline, 2 and 6 weeks
Title
Change in accuracy and reaction time
Description
Behavioral responses during computer based tasks measures cognition
Time Frame
baseline, 2 and 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participants must have signed an informed consent document indicating they understand the purpose of the study and the procedures required for the study and are willing to participate by complying with the study procedures and restrictions Participants will be male or female and aged between 18 and 50 Participants will have a Body Mass Index (BMI) 18 to 36 kg/m2 (inclusive) at the Screening Visit. The MDD participants must satisfy a diagnosis of MDD as determined by structured clinical interview for DSM-V (SCID) conducted by a psychiatrist. The MDD subtypes characterized under DSM-V also will be determined for use during post hoc tests aimed at characterizing further the heterogeneity extant within the MDD population. Participants must be sufficiently fluent in English to complete the emotional and reward tasks. Exclusion Criteria: Current use of psychotropic medication or electroconvulsive therapy (within three weeks of the baseline assessments) or psychological treatment (within 3 months of the baseline assessments) They are left handed (the site of brain activations vary depending on handedness) They are not fluent in English History of stimulant abuse (lifetime; e.g., amphetamine, cocaine), or of alcohol abuse within one year or of alcohol dependence within the lifetime. History of, or current medical conditions which in the opinion of the investigator may interfere with the scientific assessments or safety of the participant, including brain injury, epilepsy/seizures, severe hepatic cirrhosis and CNS tumour. Clinically significant abnormal values for liver function tests, clinical chemistry, urine drug screen, blood pressure measurement and ECG. It is expected that laboratory values will generally be within the normal range for the laboratory. NB clinical significance will be determined by a qualified study medic who will review the results and the participant. Current pregnancy or breastfeeding Smoker > 10 cigarettes per day or similar levels of tobacco consumption in other forms. History of smoking within 8 weeks of becoming abstinent. Any contraindication to MRI scanning, for example any metal implants in the body that include ferromagnetic objects in their bodies (e.g., metal implants, vessel clips, shrapnel injuries) or with implanted devices which may be damaged by the magnet (e.g., heart pacemakers). Participation in a psychological or medical study involving the use of medication within the last 3 months. Previous participation in any study involving the emotional test battery. Has clinically significant risk of suicidal behaviour. Medical conditions that may alter the hemodynamic parameters underlying the BOLD signal (e.g., inadequately treated hypertension, diabetes mellitus). The following exclusion criteria apply specifically to the participants in the MDD group: Any known allergy, hypersensitivity or intolerance to bupropion or its excipients. Has any contraindication to the use of bupropion. Any medical contraindication, for example conditions or treatments that may alter the absorption of bupropion such as surgical treatments involving the gut. History of or current Axis 1 DSM-V psychiatric disorder (except depression or anxiety disorders such as specific phobia or social anxiety disorder for the MDD group and drug abuse subject to the criteria outlined below).The presence of co-morbid anxiety disorders will be recorded for potential use in post hoc exploratory analyses of the influence of such conditions on the outcome measures The following criteria apply specifically to participants in the healthy control group: • History of or current Axis 1 DSM-V psychiatric disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Harmer, DPhil
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oxford
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7JX
Country
United Kingdom

12. IPD Sharing Statement

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Effects of Bupropion in Depression

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