Back to resultsCOMT Inhibition Among Individuals With Comorbid AUD/ADHD
Primary Purpose
Alcohol Use Disorder, Attention Deficit Hyperactivity Disorder
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tolcapone
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Alcohol Use Disorder
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- University of Colorado Anschutz Medical CampusRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tolcapone then Placebo
Placebo then Tolcapone
Arm 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).
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).
Outcomes
Primary Outcome Measures
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
Change in subjective response to alcohol between medication periods
Subjective High Assessment Scale (range - 0-130; higher scores = greater intoxication) after laboratory alcohol administration
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)
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
Change in selective attention-associated brain activation (fMRI) between medication periods
Multi-source interference task BOLD signal to interference trials, relative to control trials
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
Secondary Outcome Measures
Full Information
NCT ID
NCT03904498
First Posted
April 2, 2019
Last Updated
February 7, 2023
Sponsor
University of Colorado, Denver
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1. Study Identification
Unique Protocol Identification Number
NCT03904498
Brief Title
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
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 16, 2021 (Actual)
Primary Completion Date
March 1, 2025 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder, Attention Deficit Hyperactivity Disorder
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
62 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tolcapone then Placebo
Arm Type
Experimental
Arm 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).
Arm Title
Placebo then Tolcapone
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Tolcapone
Other Intervention Name(s)
Tasmar
Intervention Description
Tolcapone 100 mg tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets
Primary Outcome Measure Information:
Title
Change in alcohol-induced stimulation between medication periods
Description
Biphasic Alcohol Effects Scale stimulation score (range = 0-70; higher scores = more stimulation) after laboratory alcohol administration
Time Frame
30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Title
Change in subjective response to alcohol between medication periods
Description
Subjective High Assessment Scale (range - 0-130; higher scores = greater intoxication) after laboratory alcohol administration
Time Frame
30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Title
Change in risky decision-making after alcohol administration between medication periods
Description
Balloon Analogue Risk Task adjusted average number of pumps (higher scores = more risky decision-making)
Time Frame
30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Title
Change in cognitive-control-associated brain activation (fMRI) between medication periods
Description
Stop-signal task blood oxygenation level dependent (BOLD) signal to successful stop trials, relative to unsuccessful stop trials
Time Frame
60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Title
Change in selective attention-associated brain activation (fMRI) between medication periods
Description
Multi-source interference task BOLD signal to interference trials, relative to control trials
Time Frame
60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Title
Change in alcohol cue-elicited brain activation (fMRI) between medication periods
Description
Alcohol cue reactivity task BOLD signal to alcohol cues, relative to neutral beverage cues
Time Frame
60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joseph P Schacht, PhD
Phone
303-724-3773
Email
joseph.schacht@cuanschutz.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kristen Raymond, BA
Phone
303-724-3196
Email
kristen.raymond@cuanschutz.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph P Schacht, PhD
Organizational Affiliation
University of Colorado - Anschutz Medical Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph P Schacht, PhD
Phone
303-724-3773
Email
joseph.schacht@cuanschutz.edu
First Name & Middle Initial & Last Name & Degree
Kristen Raymond, BA
Phone
303-724-3196
Email
kristen.raymond@cuanschutz.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
COMT Inhibition Among Individuals With Comorbid AUD/ADHD
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