COMT Inhibition Among Individuals With Comorbid AUD/ADHD

NCT03904498 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 19-2335R01AA026859
• Study Type: interventional
• Target: 23
• 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, affects response to alcohol, decision-making, brain activation associated with alcohol cue reactivity, response inhibition, and selective attention, or alcohol drinking.

Conditions

Alcohol Use Disorder; Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (6)

• Change in alcohol-induced stimulation between medication periods

  Biphasic Alcohol Effects Scale stimulation score (range = 0-70; higher scores = more stimulation) after laboratory alcohol administration

  30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.

• Change in subjective response to alcohol between medication periods

  Subjective High Assessment Scale (range - 0-130; higher scores = greater intoxication) after laboratory alcohol administration

  30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.

• Change in risky decision-making after alcohol administration between medication periods

  Balloon Analogue Risk Task adjusted average number of pumps (higher scores = more risky decision-making)

  30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.

• Change in cognitive-control-associated brain activation (fMRI) between medication periods

  Stop-signal task blood oxygenation level dependent (BOLD) signal to successful stop trials, relative to unsuccessful stop trials

  60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.

• Change in selective attention-associated brain activation (fMRI) between medication periods

  Multi-source interference task BOLD signal to interference trials, relative to control trials

  60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.

• Change in alcohol cue-elicited brain activation (fMRI) between medication periods

  Alcohol cue reactivity task BOLD signal to alcohol cues, relative to neutral beverage cues

  60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.

Study Arms (2)

Tolcapone then Placebo

EXPERIMENTAL

Participants in this arm will receive tolcapone during the first medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8), and placebo during the second medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8).

Drug: Tolcapone; Drug: Placebo

Placebo then Tolcapone

EXPERIMENTAL

Participants in this arm will receive placebo during the first medication period (1 capsule on study days 1 and 2; 3 capsules on study days 3-8), and tolcapone during the second medication period (1 capsule containing 200 mg tolcapone on study days 1 and 2; 3 capsules containing a total of 600 mg tolcapone on study days 3-8).

Drug: Tolcapone; Drug: Placebo

Interventions

Tolcapone DRUG

Tolcapone 100 mg tablets

Also known as: Tasmar

Placebo then Tolcapone; Tolcapone then Placebo

Placebo DRUG

Placebo tablets

Placebo then Tolcapone; Tolcapone then Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65.
• Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder (AUD) and current Attention-Deficit/Hyperactivity Disorder (ADHD), as assessed by the Structured Clinical Interview for DSM-5 (SCID-5) or WHO-ASRS.
• Currently not engaged in, and does not want treatment for, AUD or ADHD.
• Currently not taking any medication for AUD or ADHD.
• Able to read and understand questionnaires and informed consent.
• Lives within 50 miles of the study site.

You may not qualify if:

• Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
• Any psychoactive substance use (except nicotine) within the last 30 days, as indicated by self-report and urine drug screen (UDS)
• Current DSM-5 psychotic, mood, anxiety, obsessive-compulsive, trauma-related, or eating disorder, as assessed by SCID-5.
• Current suicidal ideation or homicidal ideation.
• Current use of any psychoactive medication, as evidenced by self-report and UDS.
• 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, as evidenced by medical history and physical exam.
• 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 plasma HCG), nursing, or who are not using a reliable form of contraception.
• Current charges pending for a violent crime (not including DUI-related offenses).
• 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.
• History of neurological disease or head injury with \> 2 minutes of unconsciousness.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Alcoholism; Attention Deficit Disorder with Hyperactivity

Interventions

Tolcapone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Joseph P Schacht, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: April 5, 2019
• Study Start: August 16, 2021
• Primary Completion: March 9, 2026
• Study Completion: March 9, 2026
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)