COMT Inhibition Among Individuals With Comorbid AUD/ADHD

Phase 2

Recruiting

• Conditions: Attention Deficit Hyperactivity Disorder; Alcohol Use Disorder
• Interventions: Drug: Tolcapone; Drug: Placebo

• Registration Number: NCT03904498
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

This study evaluates the effects of an FDA-approved medication called tolcapone in people who have both Alcohol Use Disorder (AUD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The study involves seven visits over a three to four week period, including an assessment visit and two eight-day medication periods during which participants will be assigned to take, in a double-blinded fashion, both tolcapone and a placebo (three visits during each period). During two of these visits, participants will undergo a one-hour MRI scan. Participants must not be seeking treatment for AUD or ADHD and must not be currently taking any psychotropic medications, including stimulant medications for ADHD.

Study Timeline

• Study First Submitted: 2019-04-02
• Study First Submitted QC: 2019-04-03
• Study First Posted: 2019-04-05
• Study Start: 2021-08-16
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-25
• Primary Completion: 2025-03-01
• Study Completion: 2025-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 62

Inclusion Criteria

1. Age 21-65.
2. 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.
3. Currently not engaged in, and does not want treatment for, AUD or ADHD.
4. Currently not taking any medication for AUD or ADHD.
5. Able to read and understand questionnaires and informed consent.
6. Lives within 50 miles of the study site.

Read More

Exclusion Criteria

1. Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
2. Any psychoactive substance use (except nicotine) within the last 30 days, as indicated by self-report and urine drug screen (UDS)
3. Current DSM-5 psychotic, mood, anxiety, obsessive-compulsive, trauma-related, or eating disorder, as assessed by SCID-5.
4. Current suicidal ideation or homicidal ideation.
5. Current use of any psychoactive medication, as evidenced by self-report and UDS.
6. 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).
7. Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems, as evidenced by medical history and physical exam.
8. Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
9. 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.
10. Females of childbearing potential who are pregnant (by plasma HCG), nursing, or who are not using a reliable form of contraception.
11. Current charges pending for a violent crime (not including DUI-related offenses).
12. Lack of a stable living situation.
13. Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
14. Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.
15. History of neurological disease or head injury with > 2 minutes of unconsciousness.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Tolcapone then Placebo	Placebo	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).
Placebo then Tolcapone	Placebo	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).
Tolcapone then Placebo	Tolcapone	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).
Placebo then Tolcapone	Tolcapone	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).

Primary Outcome Measures

Name	Time	Method
Change in alcohol-induced stimulation between medication periods	30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.	Biphasic Alcohol Effects Scale stimulation score (range = 0-70; higher scores = more stimulation) after laboratory alcohol administration
Change in subjective response to alcohol between medication periods	30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.	Subjective High Assessment Scale (range - 0-130; higher scores = greater intoxication) after laboratory alcohol administration
Change in selective attention-associated brain activation (fMRI) between medication periods	60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.	Multi-source interference task BOLD signal to interference trials, relative to control trials
Change in risky decision-making after alcohol administration between medication periods	30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.	Balloon Analogue Risk Task adjusted average number of pumps (higher scores = more risky decision-making)
Change in cognitive-control-associated brain activation (fMRI) between medication periods	60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.	Stop-signal task blood oxygenation level dependent (BOLD) signal to successful stop trials, relative to unsuccessful stop trials
Change in alcohol cue-elicited brain activation (fMRI) between medication periods	60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.	Alcohol cue reactivity task BOLD signal to alcohol cues, relative to neutral beverage cues

Trial Locations

Locations (1)

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States