Clinical trial NCT04831684: Novel MGluR5 Modulator Effects on Alcohol Drinking and MRI Outcomes
Official title: Effects of a Novel MGluR5 Negative Allosteric Modulator on Alcohol Drinking, Neurochemistry, and Brain Reactivity to Alcohol Cues in Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Alcohol Use Disorder
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2021-04-05
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study evaluates the effects of the medication GET73 among non-treatment-seeking individuals who regularly drink alcohol. Participants in the study will take GET73 or placebo for an 8-day study. There are 4 study visits including 2 MRI scans.


Eligibility criteria: Inclusion Criteria:

1. Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol consumption, consistent with our pilot data and past iterations of the ARC).
2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder, with at least Moderate severity.
3. Reports drinking, on average, at least 20 standard alcoholic drinks per week for at least the past 3 months.
4. Currently not engaged in, and does not want treatment for, alcohol-related problems.
5. Able to read and understand questionnaires and informed consent.
6. Lives within 50 miles of the study site.
7. Able to maintain abstinence from alcohol the evening prior to appointments (without the aid of detoxification medications), as determined by self-report and breathalyzer measurements.
8. Amenable to drinking liquor in fruit juice.

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 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. Using CYP2C19 and/or CYP3A4 inhibitors or inducers in the 14 days before dosing or during the study.
6. Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
7. Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
8. History of severe alcohol withdrawal (e.g., tremor, sweating, anxiety, seizure, delirium tremens), as evidenced by self-report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).
9. Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
10. Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
11. Has hepatocellular disease indicated by elevations of SGPT (ALT) or SGOT (AST) greater than 2.5 times normal at screening.
12. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
13. Current charges pending for a violent crime (not including DUI-related offenses).
14. Lack of a stable living situation.
15. Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
16. Severe claustrophobia or extreme obesity that preclude placement in the MRI scanner.
17. Neurological disease or history of head injury with \> 2 minutes of unconsciousness.

Primary outcomes:
measure: Number of drinks consumed during bar-lab paradigm (free drinking period)
timeFrame: 165 minutes
measure: Change in Gamma aminobutyric acid (GABA) and glutamate levels
timeFrame: baseline to day 7
measure: Levels of cortical activation to visual cues of alcohol
timeFrame: baseline to day 7
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Charleston Alcohol Research Center, Institute of Psychiatry, Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: James Prisciandaro
role: PRINCIPAL_INVESTIGATOR
References: