Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control

Phase 2

Completed

• Conditions: Alcohol Use Disorder
• Interventions: Drug: Placebo; Drug: Tolcapone

• Registration Number: NCT02949934
• Lead Sponsor: Medical University of South Carolina

Brief Summary

The purpose of this study is to determine whether the catechol-O-methyltransferase (COMT) inhibitor tolcapone, relative to placebo, reduces alcohol drinking and alcohol cue-elicited brain activation and increases brain activation associated with cognitive control as a function of a participant's genotype at a polymorphism in the COMT gene.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-01
• Study First Submitted: 2016-10-26
• Study First Submitted QC: 2016-10-27
• Study First Posted: 2016-10-31
• Primary Completion: 2021-04-13
• Study Completion: 2021-04-13
• Results First Submitted: 2022-03-21
• Results First Submitted QC: 2022-03-21
• Results First Posted: 2022-04-15
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-11
• Last Update Posted: 2023-06-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol consumption).
2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder.
3. Currently not engaged in, and does not want treatment for, alcohol-related problems.
4. Able to read and understand questionnaires and informed consent.
5. Lives within 50 miles of the study site.
6. Able to maintain abstinence from alcohol for two days (without the aid of detoxification medications), as determined by self report and breathalyzer measurements.

Exclusion Criteria

1. Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
2. Any psychoactive substance use (except marijuana and nicotine) within the last 30 days, as indicated by self-report and urine drug screen. For marijuana, no use within the last seven days by verbal report and negative (or decreasing) urine tetrahydrocannibinol (THC) levels.
3. Current DSM-5 Axis I diagnosis, including major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder.
4. Current suicidal ideation or homicidal ideation.
5. Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
6. Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
7. History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced by self-report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).
8. Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
9. Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
10. Current or past hepatocellular disease, as indicated by verbal report or elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than the upper limit of the normal range at screening.
11. Females of childbearing potential who are pregnant (by urine human chorionic gonadotropin), nursing, or who are not using a reliable form of birth control.
12. Current charges pending for a violent crime (not including drinking while intoxicated).
13. Lack of a stable living situation.
14. Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
15. Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.
16. History of head injury with > 2 minutes of unconsciousness.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo/rs4680 met/met	Placebo	Placebo three times per day for eight days Individuals with the rs4680 met/met genotype
Placebo/rs4680 val/val	Placebo	Placebo three times per day for eight days Individuals with the rs4680 val/val genotype
Placebo/rs4680 val/met	Placebo	Placebo three times per day for eight days Individuals with the rs4680 val/met genotype
Tolcapone/rs4680 val/val	Tolcapone	Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/val genotype
Tolcapone/rs4680 val/met	Tolcapone	Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype
Tolcapone/rs4680 met/met	Tolcapone	Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype

Primary Outcome Measures

Name	Time	Method
Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions	Days 1-6 of study medication ingestion	Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.
Total Number of Drinks Under Controlled Conditions (Bar Lab)	2 hours during the alcohol challenge procedure	Total number of drinks, out of 8 possible, that participants chose to consume in the bar laboratory after receipt of a priming drink, targeted by sex and body weight to produce a breath alcohol concentration of 0.03 g/dL. Each of the drinks that participants chose to consume was targeted to produce a breath alcohol concentration of 0.015 g/dL. Participants were given a "bar credit" of $16 with which to "purchase" drinks, at the cost of $2/drink, and were told that any money they did not spend would be given to them the following day.

Trial Locations

Locations (1)

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States