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Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control

Primary Purpose

Alcohol Use Disorder

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tolcapone
Placebo
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Use Disorder

Eligibility Criteria

21 Years - 40 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol consumption).
  2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder.
  3. Currently not engaged in, and does not want treatment for, alcohol-related problems.
  4. Able to read and understand questionnaires and informed consent.
  5. Lives within 50 miles of the study site.
  6. Able to maintain abstinence from alcohol for two days (without the aid of detoxification medications), as determined by self report and breathalyzer measurements.

Exclusion Criteria:

  1. Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
  2. 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.
  3. 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.
  4. Current suicidal ideation or homicidal ideation.
  5. Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
  6. Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
  7. 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).
  8. Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
  9. Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
  10. 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.
  11. Females of childbearing potential who are pregnant (by urine human chorionic gonadotropin), nursing, or who are not using a reliable form of birth control.
  12. Current charges pending for a violent crime (not including drinking while intoxicated).
  13. Lack of a stable living situation.
  14. Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
  15. Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.
  16. History of head injury with > 2 minutes of unconsciousness.

Sites / Locations

  • Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Arm Label

Placebo/rs4680 val/val

Tolcapone/rs4680 val/val

Placebo/rs4680 val/met

Tolcapone/rs4680 val/met

Placebo/rs4680 met/met

Tolcapone/rs4680 met/met

Arm Description

Placebo three times per day for eight days Individuals with the rs4680 val/val genotype

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

Placebo three times per day for eight days Individuals with the rs4680 val/met genotype

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

Placebo three times per day for eight days Individuals with the rs4680 met/met genotype

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
October 26, 2016
Last Updated
May 11, 2023
Sponsor
Medical University of South Carolina
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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1. Study Identification

Unique Protocol Identification Number
NCT02949934
Brief Title
Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
May 1, 2016 (Actual)
Primary Completion Date
April 13, 2021 (Actual)
Study Completion Date
April 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of South Carolina
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 polymorphism in the COMT gene.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Use Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo/rs4680 val/val
Arm Type
Placebo Comparator
Arm Description
Placebo three times per day for eight days Individuals with the rs4680 val/val genotype
Arm Title
Tolcapone/rs4680 val/val
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo/rs4680 val/met
Arm Type
Placebo Comparator
Arm Description
Placebo three times per day for eight days Individuals with the rs4680 val/met genotype
Arm Title
Tolcapone/rs4680 val/met
Arm Type
Active Comparator
Arm Description
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
Arm Title
Placebo/rs4680 met/met
Arm Type
Placebo Comparator
Arm Description
Placebo three times per day for eight days Individuals with the rs4680 met/met genotype
Arm Title
Tolcapone/rs4680 met/met
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Tolcapone
Other Intervention Name(s)
Tasmar
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Total Number of Standard Drinks Per Day Consumed During Natural (Usual Environment) Conditions
Description
Number of standard alcoholic drinks per day that participants reported consuming, as assessed by the Timeline Follow-back method.
Time Frame
Days 1-6 of study medication ingestion
Title
Total Number of Drinks Under Controlled Conditions (Bar Lab)
Description
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.
Time Frame
2 hours during the alcohol challenge procedure
Other Pre-specified Outcome Measures:
Title
Cognitive-control-associated Brain Activation (fMRI)
Description
Magnitude of change between baseline and day 7 scan in the BOLD signal in the right inferior frontal gyrus to spatial working memory
Time Frame
7 days--change between baseline and scan on day 7
Title
Alcohol Cue-elicited Brain Activation (fMRI)
Description
Magnitude of change between baseline and day 7 scan in the right inferior frontal gyrus blood oxygenation level dependent (BOLD) signal to alcohol cues, relative to neutral beverage cues (alcohol cue reactivity task described in Schacht et al., 2013, Neuropsychopharmacology)
Time Frame
7 days--change between baseline and scan on day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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). 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.
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29403
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35523943
Citation
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.
Results Reference
derived

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Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control

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