Effects of Tolcapone on Decision Making and Alcohol Intake in Alcohol Users

Effects of Tolcapone on Decision Making and Alcohol Intake Using a Laboratory Bar in Moderate to Heavy Social Drinkers

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.

Study Overview

• Status: Completed
• Conditions: Impulsive Behavior; Alcohol Abuse
• Intervention / Treatment: Drug: Placebo; Drug: Tolcapone

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94704
      • University of California, Berkeley
    • San Francisco, California, United States, 94109
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tolcapone First, then Placebo; Tolcapone arm first: 5 days of 100 mg tolcapone TID, followed by washout period, then 5 days of placebo TID	Drug: Placebo; Drug: Tolcapone; Other Names: Tasmar
Placebo Comparator: Placebo First, then Tolcapone; Placebo arm first: 5 days placebo, followed by washout period, followed by 5 days of 100 mg tolcapone TID	Drug: Placebo; Drug: Tolcapone; Other Names: Tasmar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	A laboratory bar session is 1 hour long

Collaborators and Investigators

• Sponsor: Jennifer Mitchell
• Investigators: Principal Investigator: Jennifer Mitchell, PhD, University of California, San Francisco

Publications and helpful links

General Publications

• Coker AR, Weinstein DN, Vega TA, Miller CS, Kayser AS, Mitchell JM. The catechol-O-methyltransferase inhibitor tolcapone modulates alcohol consumption and impulsive choice in alcohol use disorder. Psychopharmacology (Berl). 2020 Oct;237(10):3139-3148. doi: 10.1007/s00213-020-05599-5. Epub 2020 Jul 2.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (Estimate): April 15, 2016

Study Record Updates

• Last Update Posted (Actual): September 21, 2020
• Last Update Submitted That Met QC Criteria: September 17, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Impulsive Behavior; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Tolcapone
• Other Study ID Numbers: Tolcapone Lab Bar

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No