Novel mGluR5 Modulator Effects on Alcohol Drinking and MRI Outcomes

Alcohol Use Disorder Clinical Trial

Official title:

Effects of a Novel mGluR5 Negative Allosteric Modulator on Alcohol Drinking, Neurochemistry, and Brain Reactivity to Alcohol Cues in Alcohol Use Disorder

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04831684
• Other study ID #: Pro00102334
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 15, 2021
• Est. completion date: April 22, 2026

Study information

• Verified date: January 2024
• Source: Medical University of South Carolina
• Contact: Sara Hix
• Phone: 843-792-0572
• Email: hixs[@]musc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: April 22, 2026
• Est. primary completion date: April 15, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alcohol Drinking
• Alcohol Use Disorder
• Alcoholism

Intervention

Drug:
• Placebo
Participants will be getting placebo for 8 days of dosing.
• GET73
Participants will be getting GET73 for 8 days of dosing.

Locations

Country	Name	City	State
United States	Charleston Alcohol Research Center, Institute of Psychiatry, Medical University of South Carolina	Charleston	South Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of South Carolina	National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of drinks consumed during bar-lab paradigm (free drinking period)		165 minutes
Primary	Change in Gamma aminobutyric acid (GABA) and glutamate levels	Acquired via spectroscopy sequence completed at baseline and day 7 scans	baseline to day 7
Primary	Levels of cortical activation to visual cues of alcohol	Acquired via functional magnetic resonance imaging completed at baseline and day 7 scans	baseline to day 7