COMT Inhibition Among Individuals With Comorbid AUD/ADHD

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

COMT Inhibition as a Potential Therapeutic Target Among Individuals With Comorbid Alcohol Use Disorder and Attention-Deficit/Hyperactivity Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03904498
• Other study ID #: 19-2335
• Secondary ID: R01AA026859
• Status: Recruiting
• Phase: Phase 2
• Start date: August 16, 2021
• Est. completion date: March 1, 2025

Study information

• Verified date: February 2024
• Source: University of Colorado, Denver
• Contact: Joseph P Schacht, PhD
• Phone: 303-724-3773
• Email: joseph.schacht[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: March 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism
• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• Tolcapone
Tolcapone 100 mg tablets
• Placebo
Placebo tablets

Locations

Country	Name	City	State
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.