Alcohol Abuse, Impulsive Behavior
Conditions
Brief summary
The purpose of this study is to determine the effects of tolcapone on decision making and alcohol intake using a laboratory bar (on-site alcohol self-administration) in alcohol drinkers.
Detailed description
The study is a 7-session, double blind, placebo-controlled crossover study of the effects of tolcapone, the COMT inhibitor, on decision making and alcohol intake using a laboratory bar in moderate to heavy social alcohol drinkers. Subjects will be moderate to heavy social users of alcohol, defined as at least 10 standard drinks per week for women and at least 14 standard drinks per week for men. There will be one screening session followed by six additional visits including 2 laboratory bar sessions. On each study drug administration day, subjects will come in to the clinic for a medication dispensation visit and instructions on when and how to take the study drug for the remainder of the study. Study drug bottles will be equipped with MEMS caps to ensure compliance. After 5 days of drug administration, subjects will return to the clinic for a laboratory bar. This session will consist of administration of a standardized laboratory bar paradigm and a series of computerized and written decision-making tasks. Subjects will then be crossed over and complete the same series of study visits on the alternate study drug.
Interventions
DRUGTolcapone
DRUGPlacebo
Sponsors
Jennifer Mitchell
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers who are 21-40 years of age * If female, 10 or more alcoholic drinks must be consumed weekly. * If male, 14 or more alcoholic drinks must be consumed weekly. * Meets DSM-V criteria for Alcohol Use Disorder (AUD). * If female, must be non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device \[IUD\], hormonal birth control, or barrier method). * Ability to read and speak English. * High school graduate. * Able and willing to provide an informed consent. * Able to understand and follow the instructions of the investigator, including the delayed discounting tasks. Residing within 5 miles of the study site.
Exclusion criteria
* Positive urine drug screen (except marijuana). * Using cocaine, stimulants (other than nicotine and caffeine), amphetamines, hallucinogens, ecstasy, opiates, sedatives, pain pills, sleeping pills. or other psychoactive drugs within 2 weeks of the start of the study (except marijuana). * Marijuana use more than 3 times/week. * Current enrollment in an alcohol, or other drug treatment program or current legal problems relating to alcohol, or other drug use. * Currently trying to quit alcohol use. * History of major alcohol related complications within the preceding 2 years (liver failure/cirrhosis, pancreatitis, esophageal varices, etc.). * Two SGPT/ALT or SGOT/AST values greater than the upper limit of normal. * Unable to pass the Standard Field Sobriety Test in a sober state (BAC = 0.00). * BAC level \>0.05% at the beginning of screening visit (within margin of error of detection). * Regular use of any of the drugs on the tolcapone contraindications list OR within 2 weeks of drug administration. * Severe low blood (\< 90/50) pressure or uncontrolled high blood pressure (\>160/100). Allergy or intolerance to tolcapone. * Subject has received an investigational drug within 30 days of the screening visit. * Subject is considered unsuitable for the study in the opinion of the investigator or clinician for any other reason (such as an Axis II personality disorder that makes the subject unable to comply with study instructions, per the Clinician's judgement.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Drinks Consumed in a Laboratory Bar Session | A laboratory bar session is 1 hour long | Number of drinks consumed in a laboratory bar session (out of a maximum of 4 drinks available) following either placebo or tolcapone administration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tolcapone First Tolcapone arm first: 5 days of 100 mg tolcapone TID, followed by washout period, then 5 days of placebo TID
Tolcapone
Placebo | 23 |
| Placebo First Placebo arm first: 5 days placebo, followed by washout period, followed by 5 days of 100 mg tolcapone TID
Tolcapone
Placebo | 28 |
| Total | 51 |
Baseline characteristics
| Characteristic | Tolcapone First | Placebo First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 28 Participants | 51 Participants |
| Age, Continuous | 24.4 years | 27.3 years | 25.98 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 23 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 18 Participants | 33 Participants |
| Region of Enrollment United States | 23 participants | 28 participants | 51 participants |
| Self-reported alcoholic drinks / week | 24.79 alcoholic drinks / week | 18.13 alcoholic drinks / week | 21.13 alcoholic drinks / week |
| Sex: Female, Male Female | 8 Participants | 14 Participants | 22 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 60 | 0 / 57 |
| other Total, other adverse events | 0 / 60 | 0 / 57 |
| serious Total, serious adverse events | 0 / 60 | 0 / 57 |
Outcome results
Primary
Number of Drinks Consumed in a Laboratory Bar Session
Number of drinks consumed in a laboratory bar session (out of a maximum of 4 drinks available) following either placebo or tolcapone administration.
Time frame: A laboratory bar session is 1 hour long
Population: Completers were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tolcapone First, Then Placebo | Number of Drinks Consumed in a Laboratory Bar Session | Drinks on Placebo | 2.69 drinks | Standard Deviation 1.45 |
| Tolcapone First, Then Placebo | Number of Drinks Consumed in a Laboratory Bar Session | Drinks on tolcapone | 2.73 drinks | Standard Deviation 1.38 |
| Placebo First, Then Tolcapone | Number of Drinks Consumed in a Laboratory Bar Session | Drinks on Placebo | 2.96 drinks | Standard Deviation 1.1 |
| Placebo First, Then Tolcapone | Number of Drinks Consumed in a Laboratory Bar Session | Drinks on tolcapone | 2.39 drinks | Standard Deviation 1.66 |