COMT Inhibition Among Individuals With Comorbid AUD/ADHD

University of Colorado Denver (CU Denver)

Status and phase: Enrolling; Phase 2

Conditions: Attention Deficit Hyperactivity Disorder; Alcohol Use Disorder

Treatments: Drug: Placebo; Drug: Tolcapone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03904498

R01AA026859 (U.S. NIH Grant/Contract)

19-2335

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 estimated patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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62 participants in 2 patient groups

Tolcapone then Placebo

Experimental group

Description:

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).

Treatment:

Drug: Tolcapone

Drug: Placebo

Placebo then Tolcapone

Experimental group

Description:

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).

Treatment:

Drug: Tolcapone

Drug: Placebo