Alcohol Use DisorderPhase 2NCT03904498
COMT Inhibition Among Individuals With Comorbid AUD/ADHD
A Phase 2 study testing Tolcapone in people with Alcohol Use Disorder and Attention Deficit Hyperactivity Disorder, run by University of Colorado, Denver at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Alcohol Use Disorder, Attention Deficit Hyperactivity Disorder
- What is being tested?
- Tolcapone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2021to 9 Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
About this study
Official title: COMT Inhibition as a Potential Therapeutic Target Among Individuals With Comorbid Alcohol Use Disorder and Attention-Deficit/Hyperactivity Disorder
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.
Read the 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.
- Being tested
- Tolcapone, Placebo
- Medical subject headings
- Alcoholism, Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolcaponeDrug
Also called Tasmar
Tolcapone 100 mg tablets
PlaceboDrug
Placebo tablets
| Study group | Role | What they receive |
|---|---|---|
| Tolcapone then Placebo | Experimental | 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). Receives: Drug: Tolcapone; Drug: Placebo |
| Placebo then Tolcapone | Experimental | 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). Receives: Drug: Tolcapone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
Change in subjective response to alcohol between medication periods
Subjective High Assessment Scale (range - 0-130; higher scores = greater intoxication) after laboratory alcohol administration
Measured: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
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)
Measured: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.
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
Measured: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Change in selective attention-associated brain activation (fMRI) between medication periods
Multi-source interference task BOLD signal to interference trials, relative to control trials
Measured: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
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
Measured: 60 minutes after medication ingestion on Day 2 of each medication period. Each medication period is 8 days long.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study start16 Aug 2021
- Primary completion9 Mar 2026
- Study completion9 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Joseph P Schacht, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03904498
- Sponsor's protocol ID
- 19-2335
- Other IDs
- R01AA026859
- Status last verified
- Apr 2026
- First submitted
- 2 Apr 2019
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMT Inhibition as a Potential Therapeutic Target Among Individuals With Comorbid Alcohol Use Disorder and Attention-Deficit/Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT03904498
- Acronym / sponsor ID
- 19-2335
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 16 Aug 2021 (actual)
- Primary completion
- 9 Mar 2026 (actual)
- Study completion
- 9 Mar 2026 (actual)
- First posted
- 5 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolcapone then Placebo | Experimental | Drug: Tolcapone, Drug: PlaceboParticipants 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 | Experimental | Drug: Tolcapone, Drug: PlaceboParticipants 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). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolcaponeAlso: TasmarTolcapone 100 mg tablets | Drug | Placebo then Tolcapone, Tolcapone then Placebo |
| PlaceboPlacebo tablets | Drug | Placebo then Tolcapone, Tolcapone then Placebo |
Primary outcome
Change in alcohol-induced stimulation between medication periods
Time frame: 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
Time frame: 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 risky decision-making after alcohol administration between medication periods
Time frame: 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
Time frame: 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 selective attention-associated brain activation (fMRI) between medication periods
Time frame: 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 alcohol cue-elicited brain activation (fMRI) between medication periods
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph P Schacht, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tolcapone in people with Alcohol Use Disorder and Attention Deficit Hyperactivity Disorder, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in alcohol-induced stimulation between medication periods (time frame: 30 minutes after laboratory alcohol administration on Day 1 of each medication period. Each medication period is 8 days long.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026.