Dopaminergic Modulation of Frontostriatal Function With a Dopamine Agonist and COMT Inhibitor
Primary Purpose
Addiction
Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Tolcapone
Placebo
Bromocriptine
Sponsored by
About this trial
This is an interventional basic science trial for Addiction
Eligibility Criteria
Inclusion Criteria:
- Age between 18 and 50 years.
- Subject is right-handed.
- If female, subject is non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device (IUD), hormonal birth control or barrier method).
- Subject is able to read and speak English.
- Subject is a high school graduate.
- Subject is able and willing to provide written and informed consent.
- Subject is able to understand and follow the instructions of the investigator, and understand all ratings scales.
- Subject is in good health.
Exclusion Criteria
- Using cocaine, stimulants (other than THC, nicotine, & caffeine)amphetamines, hallucinogens, "ecstasy", opiates, sedatives, pain pills, sleeping pills or other psychoactive drugs within two weeks of the start of the study OR more than 10 times in the last year.
- Has a current dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol.
- Clinically significant medical or psychiatric illness requiring treatment as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician.
- Subject has a history of major alcohol related complications within the proceeding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.)
- Liver function test ≥ 3 times normal upper limit.
- BAC level > 0.05% at the beginning of screening visit (within margin of error of detection).
- Has a neurological dysfunction or psychiatric disorder.
- Has severe low blood pressure.
- Has uncontrolled high blood pressure.
- Regular use of any of the drugs on the tolcapone or entacapone contraindications list OR within 2 weeks of drug administration.
- Regular use of SSRIs.
- Has an allergy or intolerance to tolcapone or entacapone.
- Subject has received an investigational drug within 30 days of screening visit.
- Subject is considered unsuitable for the study in the opinion of the investigator or study physician for any other reason.
MRI Exclusion Criteria:
- The subject has metal (metal plates, pins, wires or screws, artificial limb, joint replacement or anything that might have been inserted during an operation) in his/her body.
- Subject has a pacemaker, defibrillator, stent, or any metal implants related to heart/blood flow problems.
- Subject has worked with metals (ie. metallurgy, metal shaving, welding, soldering, etc).
- Subject has been wounded with anything metal (bullet, shrapnel or metal filling).
- Has ever gotten a piece of metal in the eye.
- Has tattoos done with ink containing metal or permanent eyeliner.
- Wears color contact lenses.
- Has a hearing problem or hearing aid, cochlear implant or past ear surgery.
- Has any irremovable dental bridges, dental plates, metal caps or any other non-removable metal in the mouth.
- The subject is claustrophobic.
- The subject is pregnant. (women only)
- Has a IUD. (women only)
- Significantly overweight.
Sites / Locations
- University of California, Berkeley
- University of California, San Francisco
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Experimental: Tolcapone
Comparator: Placebo
Experimental: Bromocriptine
Arm Description
Drug: Tolcapone 200mg (single dose) administered at study visit
Drug: Placebo for tolcapone administered at study visit
Drug: Bromocriptine 1.25mg (single dose) administered at study visit
Outcomes
Primary Outcome Measures
Measure Effects of Placebo,Tolcapone, Bromocriptine on Reaction Time
Participants will play the Dictator Game. Behavioral responses to the game during each arm (placebo, tolcapone, and bromocriptine) will be measured by subject reaction time .
Measure Effects of Placebo,Tolcapone, Bromocriptine on Accuracy
Participants will play the Dictator Game. Behavioral responses to the game during each arm (placebo, tolcapone, and bromocriptine) will be measured by subject accuracy (correct or incorrect responses).
Secondary Outcome Measures
Measure Observed Changes in Resting State Neural Activity
Resting-state data will be processed off-line using neuroimaging analysis software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. Changes in regional brain activity will be measured during the placebo, tolcapone and bromocriptine conditions.
Measure Observed Changes in Task Dependent Neural Activity
Task dependent fMRI data will be processed off-line using neuroimaging analysis software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. Changes in task dependent brain activity will be measured during the placebo, tolcapone and bromocriptine conditions.
Full Information
NCT ID
NCT02929485
First Posted
September 28, 2016
Last Updated
November 12, 2021
Sponsor
University of California, Berkeley
Collaborators
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT02929485
Brief Title
Dopaminergic Modulation of Frontostriatal Function With a Dopamine Agonist and COMT Inhibitor
Official Title
Dopaminergic Modulation of Frontostriatal Function With a Dopamine Agonist and COMT Inhibitor
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Withdrawn
Study Start Date
July 2013 (Anticipated)
Primary Completion Date
January 31, 2018 (Anticipated)
Study Completion Date
January 31, 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Berkeley
Collaborators
University of California, San Francisco
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this study, the investigators are looking at how people make decisions about reward-related items, both monetary and food related after taking either the dopamine agonist bromocriptine or the COMT inhibitor tolcapone, in healthy control subjects. Subjects will fill self-report questionnaires and undergo an MRI scan.
Detailed Description
The investigators aim to understand how the brain's dopamine system impacts monetary and food-related decision making. The investigators aim to use tolcapone and bromocriptine due to the temporary change in the levels of dopamine in the brain. The investigators also aim to determine if genetics, personality traits, or a family history of alcoholism change how these drugs affect decision making.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Addiction
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Tolcapone
Arm Type
Experimental
Arm Description
Drug: Tolcapone 200mg (single dose) administered at study visit
Arm Title
Comparator: Placebo
Arm Type
Placebo Comparator
Arm Description
Drug: Placebo for tolcapone administered at study visit
Arm Title
Experimental: Bromocriptine
Arm Type
Experimental
Arm Description
Drug: Bromocriptine 1.25mg (single dose) administered at study visit
Intervention Type
Drug
Intervention Name(s)
Tolcapone
Other Intervention Name(s)
Tasmar
Intervention Description
Tolcapone 200mg (single dose) administered at study visit
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo (200mg) administered at study visit
Intervention Type
Drug
Intervention Name(s)
Bromocriptine
Other Intervention Name(s)
Parlodel
Intervention Description
Drug: Bromocriptine 1.25 mg (single dose) administered at study visit
Primary Outcome Measure Information:
Title
Measure Effects of Placebo,Tolcapone, Bromocriptine on Reaction Time
Description
Participants will play the Dictator Game. Behavioral responses to the game during each arm (placebo, tolcapone, and bromocriptine) will be measured by subject reaction time .
Time Frame
3 weeks
Title
Measure Effects of Placebo,Tolcapone, Bromocriptine on Accuracy
Description
Participants will play the Dictator Game. Behavioral responses to the game during each arm (placebo, tolcapone, and bromocriptine) will be measured by subject accuracy (correct or incorrect responses).
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Measure Observed Changes in Resting State Neural Activity
Description
Resting-state data will be processed off-line using neuroimaging analysis software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. Changes in regional brain activity will be measured during the placebo, tolcapone and bromocriptine conditions.
Time Frame
3 weeks
Title
Measure Observed Changes in Task Dependent Neural Activity
Description
Task dependent fMRI data will be processed off-line using neuroimaging analysis software according to standard procedures for image slice-timing correction, realignment, normalization and smoothing. Changes in task dependent brain activity will be measured during the placebo, tolcapone and bromocriptine conditions.
Time Frame
3 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:
Age between 18 and 50 years.
Subject is right-handed.
If female, subject is non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device (IUD), hormonal birth control or barrier method).
Subject is able to read and speak English.
Subject is a high school graduate.
Subject is able and willing to provide written and informed consent.
Subject is able to understand and follow the instructions of the investigator, and understand all ratings scales.
Subject is in good health.
Exclusion Criteria
Using cocaine, stimulants (other than THC, nicotine, & caffeine)amphetamines, hallucinogens, "ecstasy", opiates, sedatives, pain pills, sleeping pills or other psychoactive drugs within two weeks of the start of the study OR more than 10 times in the last year.
Has a current dependence on, or addiction to any psychoactive drug (except nicotine or caffeine) including alcohol.
Clinically significant medical or psychiatric illness requiring treatment as determined by screening blood tests, medical history, and physical exam performed or reviewed by the study physician.
Subject has a history of major alcohol related complications within the proceeding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.)
Liver function test ≥ 3 times normal upper limit.
BAC level > 0.05% at the beginning of screening visit (within margin of error of detection).
Has a neurological dysfunction or psychiatric disorder.
Has severe low blood pressure.
Has uncontrolled high blood pressure.
Regular use of any of the drugs on the tolcapone or entacapone contraindications list OR within 2 weeks of drug administration.
Regular use of SSRIs.
Has an allergy or intolerance to tolcapone or entacapone.
Subject has received an investigational drug within 30 days of screening visit.
Subject is considered unsuitable for the study in the opinion of the investigator or study physician for any other reason.
MRI Exclusion Criteria:
The subject has metal (metal plates, pins, wires or screws, artificial limb, joint replacement or anything that might have been inserted during an operation) in his/her body.
Subject has a pacemaker, defibrillator, stent, or any metal implants related to heart/blood flow problems.
Subject has worked with metals (ie. metallurgy, metal shaving, welding, soldering, etc).
Subject has been wounded with anything metal (bullet, shrapnel or metal filling).
Has ever gotten a piece of metal in the eye.
Has tattoos done with ink containing metal or permanent eyeliner.
Wears color contact lenses.
Has a hearing problem or hearing aid, cochlear implant or past ear surgery.
Has any irremovable dental bridges, dental plates, metal caps or any other non-removable metal in the mouth.
The subject is claustrophobic.
The subject is pregnant. (women only)
Has a IUD. (women only)
Significantly overweight.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Kayser, MD,PhD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, Berkeley
City
Berkeley
State/Province
California
ZIP/Postal Code
94704
Country
United States
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Dopaminergic Modulation of Frontostriatal Function With a Dopamine Agonist and COMT Inhibitor
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