Alcohol Use DisorderPhase 2NCT02949934
Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control
A Phase 2 study testing Tolcapone in people with Alcohol Use Disorder, run by Medical University of South Carolina 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, reduces alcohol drinking and alcohol cue-elicited brain activation and increases brain activation associated with cognitive control as a function of a participant's genotype at a… Read more about this study
- Who is it for?
- Ages 21 to 40 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Tolcapone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2016to 13 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol consumption).
- Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder.
- Currently not engaged in, and does not want treatment for, alcohol-related problems.
- Able to read and understand questionnaires and informed consent.
- Lives within 50 miles of the study site.
- Able to maintain abstinence from alcohol for two days (without the aid of detoxification medications), as determined by self report and breathalyzer measurements.
Who cannot join
- Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
- Any psychoactive substance use (except marijuana and nicotine) within the last 30 days, as indicated by self-report and urine drug screen. For marijuana, no use within the last seven days by verbal report and negative (or decreasing) urine tetrahydrocannibinol (THC) levels.
- Current DSM-5 Axis I diagnosis, including major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder.
- Current suicidal ideation or homicidal ideation.
- Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
- Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
Show all 16Show fewer
- 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 that would impair participation or limit medication ingestion.
- 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 urine human chorionic gonadotropin), nursing, or who are not using a reliable form of birth control.
- Current charges pending for a violent crime (not including drinking while intoxicated).
- 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 head injury with > 2 minutes of unconsciousness.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical University of South Carolina
Charleston, South Carolina, 29403
About this study
The purpose of this study is to determine whether the catechol-O-methyltransferase (COMT) inhibitor tolcapone, relative to placebo, reduces alcohol drinking and alcohol cue-elicited brain activation and increases brain activation associated with cognitive control as a function of a participant's genotype at a polymorphism in the COMT gene.
- Conditions
- Alcohol Use Disorder
- Being tested
- Tolcapone, Placebo
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolcaponeDrug
Also called Tasmar
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Placebo/rs4680 val/val | Placebo comparator | Placebo three times per day for eight days
Individuals with the rs4680 val/val genotype Receives: Drug: Placebo |
| Tolcapone/rs4680 val/val | Active comparator | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days
Individuals with the rs4680 val/val genotype Receives: Drug: Tolcapone |
| Placebo/rs4680 val/met | Placebo comparator | Placebo three times per day for eight days
Individuals with the rs4680 val/met genotype Receives: Drug: Placebo |
| Tolcapone/rs4680 val/met | Active comparator | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days
Individuals with the rs4680 val/met genotype Receives: Drug: Tolcapone |
| Placebo/rs4680 met/met | Placebo comparator | Placebo three times per day for eight days
Individuals with the rs4680 met/met genotype Receives: Drug: Placebo |
| Tolcapone/rs4680 met/met | Active comparator | Tolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days
Individuals with the rs4680 met/met genotype Receives: Drug: Tolcapone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions
Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.
Measured: Days 1-6 of study medication ingestion
Total Number of Drinks Under Controlled Conditions (Bar Lab)
Total number of drinks, out of 8 possible, that participants chose to consume in the bar laboratory after receipt of a priming drink, targeted by sex and body weight to produce a breath alcohol concentration of 0.03 g/dL. Each of the drinks that participants chose to consume was targeted to produce a breath alcohol concentration of 0.015 g/dL. Participants were given a "bar credit" of $16 with which to "purchase" drinks, at the cost of $2/drink, and were told that any money they did not spend would be given to them the following day.
Measured: 2 hours during the alcohol challenge procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2016 (estimated)
- Study start1 May 2016
- Primary completion13 Apr 2021
- Study completion13 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Raymond F. Anton, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02949934
- Sponsor's protocol ID
- Pro00050157
- Other IDs
- P50AA010761
- Status last verified
- May 2023
- First submitted
- 26 Oct 2016
- Last updated
- 9 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Schacht JP, Yeongbin Im, Hoffman M, Voronin KE, Book SW, Anton RF. Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone. Neuropsychopharmacology. 2022 Oct;47(11):1953-1960. doi: 10.1038/s41386-022-01335-z. Epub 2022 May 6.
PubMed 35523943
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control
- ClinicalTrials.gov ID
- NCT02949934
- Acronym / sponsor ID
- Pro00050157
- Conditions
- Alcohol Use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 1 May 2016 (actual)
- Primary completion
- 13 Apr 2021 (actual)
- Study completion
- 13 Apr 2021 (actual)
- First posted
- 31 Oct 2016 (estimated)
- Results
- Posted 15 Apr 2022
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, reduces alcohol drinking and alcohol cue-elicited brain activation and increases brain activation associated with cognitive control as a function of a participant's genotype at a polymorphism in the COMT gene.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo/rs4680 val/val | Placebo comparator | Drug: PlaceboPlacebo three times per day for eight days Individuals with the rs4680 val/val genotype |
| Tolcapone/rs4680 val/val | Active comparator | Drug: TolcaponeTolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/val genotype |
| Placebo/rs4680 val/met | Placebo comparator | Drug: PlaceboPlacebo three times per day for eight days Individuals with the rs4680 val/met genotype |
| Tolcapone/rs4680 val/met | Active comparator | Drug: TolcaponeTolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 val/met genotype |
| Placebo/rs4680 met/met | Placebo comparator | Drug: PlaceboPlacebo three times per day for eight days Individuals with the rs4680 met/met genotype |
| Tolcapone/rs4680 met/met | Active comparator | Drug: TolcaponeTolcapone 100 mg three times per day for three days Tolcapone 200 mg three times per day for five days Individuals with the rs4680 met/met genotype |
Who may qualify
- Ages
- 21 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol consumption).
- Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder.
- Currently not engaged in, and does not want treatment for, alcohol-related problems.
- Able to read and understand questionnaires and informed consent.
- Lives within 50 miles of the study site.
Key exclusion criteria (16 listed)
- Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
- Any psychoactive substance use (except marijuana and nicotine) within the last 30 days, as indicated by self-report and urine drug screen. For marijuana, no use within the last seven days by verbal report and negative (or decreasing) urine tetrahydrocannibinol (THC) levels.
- Current DSM-5 Axis I diagnosis, including major depression, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder.
- Current suicidal ideation or homicidal ideation.
- Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
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: Tasmar | Drug | Tolcapone/rs4680 met/met, Tolcapone/rs4680 val/met, Tolcapone/rs4680 val/val |
| Placebo | Drug | Placebo/rs4680 met/met, Placebo/rs4680 val/met, Placebo/rs4680 val/val |
Primary outcome
Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions
Time frame: Days 1-6 of study medication ingestion
Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.
Total Number of Drinks Under Controlled Conditions (Bar Lab)
Time frame: 2 hours during the alcohol challenge procedure
Total number of drinks, out of 8 possible, that participants chose to consume in the bar laboratory after receipt of a priming drink, targeted by sex and body weight to produce a breath alcohol concentration of 0.03 g/dL. Each of the drinks that participants chose to consume was targeted to produce a breath alcohol concentration of 0.015 g/dL. Participants were given a "bar credit" of $16 with which to "purchase" drinks, at the cost of $2/drink, and were told that any money they did not spend would be given to them the following day.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35523943Schacht JP, Yeongbin Im, Hoffman M, Voronin KE, Book SW, Anton RF. Effects of pharmacological and genetic regulation of COMT activity in alcohol use disorder: a randomized, placebo-controlled trial of tolcapone. Neuropsychopharmacology. 2022 Oct;47(11):1953-1960. doi: 10.1038/s41386-022-01335-z. Epub 2022 May 6.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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, run by Medical University of South Carolina 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 16 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 9 Jun 2023. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 15 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions (time frame: Days 1-6 of study medication ingestion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02949934, which also lists 1 linked publication.
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 9 Jun 2023.