Novel mGluR5 Modulator Effects on Alcohol Drinking and MRI Outcomes

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

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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: GET73

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Charleston Alcohol Research Center, Institute of Psychiatry, Medical University of South Carolina

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group B	Drug: GET73; Participants will be getting GET73 for 8 days of dosing.
Placebo Comparator: Group A	Drug: Placebo; Participants will be getting placebo for 8 days of dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of drinks consumed during bar-lab paradigm (free drinking period)		165 minutes
Change in Gamma aminobutyric acid (GABA) and glutamate levels	Acquired via spectroscopy sequence completed at baseline and day 7 scans	baseline to day 7
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

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: James Prisciandaro, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): December 29, 2025
• Study Completion (Actual): December 29, 2025

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism
• Other Study ID Numbers: Pro00102334

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Per NOT-AA-19-020, this study will submit and share data with NIAAA Data Archive, a data repository housed within the NIMH Data Archive. This includes broad sharing of all research subjects' de-identified data.
• IPD Sharing Time Frame: De-identified participant data will be uploaded to the NIMH Data Archive twice yearly (by April 1 and October 1) during the course of this study, and will remain available with no end date.
• IPD Sharing Access Criteria: Data and supporting documentation submitted to the NIMH Data Archive may be accessed and used broadly by approved users for research and other activities as authorized by and consistent with law.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No