Clinical trial NCT03904498: COMT Inhibition Among Individuals With Comorbid AUD/ADHD
Official title: COMT Inhibition as a Potential Therapeutic Target Among Individuals With Comorbid Alcohol Use Disorder and Attention-Deficit/Hyperactivity Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Alcohol Use Disorder
Attention Deficit Hyperactivity Disorder
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2019-04-05
Enrollment: 62
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in alcohol-induced stimulation between medication periods
timeFrame: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
measure: Change in subjective response to alcohol between medication periods
timeFrame: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
measure: Change in risky decision-making after alcohol administration between medication periods
timeFrame: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
measure: Change in cognitive-control-associated brain activation (fMRI) between medication periods
timeFrame: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
measure: Change in selective attention-associated brain activation (fMRI) between medication periods
timeFrame: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
measure: Change in alcohol cue-elicited brain activation (fMRI) between medication periods
timeFrame: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Joseph P Schacht, PhD
role: PRINCIPAL_INVESTIGATOR
References: