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

NCT02949934 | Completed Phase 2 Results DMC

• 2 other identifiers: Pro00050157P50AA010761
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Use Disorder

Outcome Measures

Primary Outcomes (2)

• Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions

  Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.

  Days 1-6 of study medication ingestion

• Total Number of Drinks Under Controlled Conditions (Bar Lab)

  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.

  2 hours during the alcohol challenge procedure

Other Outcomes (2)

• Cognitive-control-associated Brain Activation (fMRI)

  7 days--change between baseline and scan on day 7

• Alcohol Cue-elicited Brain Activation (fMRI)

  7 days--change between baseline and scan on day 7

Study Arms (6)

Placebo/rs4680 val/val

PLACEBO COMPARATOR

Placebo three times per day for eight days Individuals with the rs4680 val/val genotype

Drug: Placebo

Tolcapone/rs4680 val/val

ACTIVE COMPARATOR

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

Drug: Tolcapone

Placebo/rs4680 val/met

PLACEBO COMPARATOR

Placebo three times per day for eight days Individuals with the rs4680 val/met genotype

Drug: Placebo

Tolcapone/rs4680 val/met

ACTIVE COMPARATOR

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

Drug: Tolcapone

Placebo/rs4680 met/met

PLACEBO COMPARATOR

Placebo three times per day for eight days Individuals with the rs4680 met/met genotype

Drug: Placebo

Tolcapone/rs4680 met/met

ACTIVE COMPARATOR

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

Drug: Tolcapone

Interventions

Tolcapone DRUG

Also known as: Tasmar

Tolcapone/rs4680 met/met; Tolcapone/rs4680 val/met; Tolcapone/rs4680 val/val

Placebo DRUG

Placebo/rs4680 met/met; Placebo/rs4680 val/met; Placebo/rs4680 val/val

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
• 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.
• 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.
• Current suicidal ideation or homicidal ideation.
• Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
• Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
• 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).
• Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
• Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
• 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.
• Females of childbearing potential who are pregnant (by urine human chorionic gonadotropin), nursing, or who are not using a reliable form of birth control.
• Current charges pending for a violent crime (not including drinking while intoxicated).
• Lack of a stable living situation.
• Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
• Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29403, United States

Location

Related Publications (1)

• Schacht JP, Yeongbin Im, Hoffman M, Voronin KE, Book SW, Anton RF. Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone. Neuropsychopharmacology. 2022 Oct;47(11):1953-1960. doi: 10.1038/s41386-022-01335-z. Epub 2022 May 6.

  PMID: 35523943 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitrophenols; Phenols; Ketones; Nitro Compounds

Results Point of Contact

• Title: Joseph P. Schacht, Ph.D.
• Organization: University of Colorado School of Medicine

joseph.schacht@cuanschutz.edu

(303) 724-3773

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Distinguished University Professor

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: October 31, 2016
• Study Start: May 1, 2016
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: June 9, 2023
• Results First Posted: April 15, 2022

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)