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

• Sponsor: Jennifer Mitchell (Other)
• Overall Status: Completed
• CT.gov ID: NCT02740582
• Collaborator: (none)
• Enrollment: 62
• Locations: 2
• Arms: 2
• Actual Duration (Months): 37
• Patients Per Site: 31
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Abuse; Impulsive Behavior	Drug: Tolcapone; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: Effects of Tolcapone on Decision Making and Alcohol Intake Using a Laboratory Bar in Moderate to Heavy Social Drinkers
• Actual Study Start Date: Oct 1, 2016
• Actual Primary Completion Date: Sep 1, 2019
• Actual Study Completion Date: Nov 1, 2019

Arms and Interventions

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: Tolcapone; Other Names: Tasmar ; Drug: Placebo
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: Tolcapone; Other Names: Tasmar ; Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts 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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Berkeley	Berkeley	California	United States	94704
2	University of California, San Francisco	San Francisco	California	United States	94109

Sponsors and Collaborators

• Jennifer Mitchell

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 1, 2019

More Information

Publications

None provided.

• Responsible Party: Jennifer Mitchell, Associate Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02740582
• Other Study ID Numbers: Tolcapone Lab Bar
• First Posted: Apr 15, 2016
• Last Update Posted: Sep 21, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alcoholism; Impulsive Behavior; Alcohol Drinking; Tolcapone

Study Results

Participant Flow

Arm/Group Title	Tolcapone First	Placebo First
Arm/Group Description	Tolcapone arm first: 5 days of 100 mg tolcapone TID, followed by washout period, then 5 days of placebo TID	Placebo arm first: 5 days placebo, followed by washout period, followed by 5 days of 100 mg tolcapone TID
Period Title: First Intervention
STARTED	29	33
COMPLETED	24	31
NOT COMPLETED	5	2
Period Title: First Intervention
STARTED	24	31
COMPLETED	24	31
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	24	31
COMPLETED	23	28
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Tolcapone First	Placebo First	Total
Arm/Group Description	Tolcapone arm first: 5 days of 100 mg tolcapone TID, followed by washout period, then 5 days of placebo TID Tolcapone Placebo	Placebo arm first: 5 days placebo, followed by washout period, followed by 5 days of 100 mg tolcapone TID Tolcapone Placebo	Total of all reporting groups
Overall Participants	23	28	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	23 100%	28 100%	51 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	24.4	27.3	25.98
Sex: Female, Male (Count of Participants)
Female	8 34.8%	14 50%	22 43.1%
Male	15 65.2%	14 50%	29 56.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 13%	5 17.9%	8 15.7%
Not Hispanic or Latino	20 87%	23 82.1%	43 84.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	5 21.7%	4 14.3%	9 17.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 3.6%	1 2%
Black or African American	1 4.3%	1 3.6%	2 3.9%
White	15 65.2%	18 64.3%	33 64.7%
More than one race	2 8.7%	4 14.3%	6 11.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	23 100%	28 100%	51 100%
Self-reported alcoholic drinks / week (alcoholic drinks / week) [Mean (Full Range) ]
Mean (Full Range) [alcoholic drinks / week]	24.79	18.13	21.13

Outcome Measures

1. Primary Outcome

Title	Number of Drinks Consumed in a Laboratory Bar Session
Description	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

Outcome Measure Data

Analysis Population Description

Completers were analyzed

Arm/Group Title	Tolcapone First, Then Placebo	Placebo First, Then Tolcapone
Arm/Group Description	Tolcapone arm first: 5 days of 100 mg tolcapone TID, followed by washout period, then 5 days of placebo TID Tolcapone Placebo	Placebo arm first: 5 days placebo, followed by washout period, followed by 5 days of 100 mg tolcapone TID Tolcapone Placebo
Measure Participants	23	28
Drinks on Placebo	2.69 (1.45)	2.96 (1.1)
Drinks on tolcapone	2.73 (1.38)	2.39 (1.66)

Adverse Events

Time Frame	From enrollment through study completion, an average of 3 weeks
Adverse Event Reporting Description	The study staff will probe, via effects scale survey completed by subjects and discussion with the subject where necessary, for the occurrence of AEs during each subject visit. Study staff will continue to follow up with the subject daily until the matter is resolved (AE has decreased to 2).
Arm/Group Title	Tolcapone		Placebeo
Arm/Group Description	Adverse Events Groups are being reported "per intervention" (e.g., "Tolcapone" and "Placebo") rather than based on group in the cross over study. Tolcapone Group here reflect all participants who received Tolcapone during the study, regardless of order.		Adverse Events Groups are being reported "per intervention" (e.g., "Tolcapone" and "Placebo") rather than based on group in the cross over study. Placebo Group here reflect all participants who received Placebo during the study, regardless of order.
All Cause Mortality
	Tolcapone		Placebeo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/57 (0%)
Serious Adverse Events
	Tolcapone		Placebeo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Tolcapone		Placebeo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/57 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.