Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant

NCT ID: NCT05203965

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-17
• Study Completion Date: 2026-07-31

Brief Summary

The purpose of this study is to evaluate the role of Mavoglurant in clarifying the neurobiology of alcoholism risk. This is a one-site, randomized, within subjects, counterbalanced double-blind study of a single dose (200mg) of Mavoglurant and placebo.

Detailed Description

This project explores the effects of 1 dose of Mavoglurant, an experimental non-competitive antagonist to metabotropic glutamate receptor-5 (mGlur5) developed by Novartis, in a double-blind, randomized, counterbalanced manner on alcoholism risk-relevant tasks. Drug/placebo will be administered on 2 separate visits separated by 1 week. More specifically, this project examines 4 functional MRI tasks related to different aspects of reward and/or impulsivity-related behavior in different contexts, compares the underlying neural circuitry across tasks, and uses a pharmacologic probe of the glutamatergic system to examine N-methyl-D-Aspartate and Dopamine (NMDA/DA) interactions. The combined measures provide the opportunity to advance our understanding of specific aspects of brain function related to familial alcoholism vulnerability in an already well characterized population as some members evolve into alcohol abuse. In addition, as well as conventional within-task analyses, functional network connectivity and allied approaches will be used to examine brain networks across the tasks.

Conditions

Familial Alcoholism Vulnerability

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

FHP; Mavoglurant-Placebo

Family History Positive (FHP) for alcoholism will be given a single dose of AFQ056 (200 mg) then placebo in two separate experimental study visits separated by 1 week. Drug and Placebo administered 2 hours prior to the MRI and other measures.

Group Type: EXPERIMENTAL

Mavoglurant (AFQ056)

Intervention Type: DRUG

Two 100mg tablets of Mavoglurant will be administered on the morning of one of the two experimental days by a RN or the physician investigator.

Placebo

Intervention Type: DRUG

Two matching tablets of placebo will be administered on the morning of one of the two experimental days by an RN or the physician investigator.

FHP; Placebo-Mavoglurant

Family History Positive (FHP) or alcoholism will be given a single dose of placebo then AFQ056 (200 mg) in two separate experimental study visits separated by 1 week. Drug and Placebo administered 2 hours prior to the MRI and other measures.

Group Type: EXPERIMENTAL

Mavoglurant (AFQ056)

Intervention Type: DRUG

Two 100mg tablets of Mavoglurant will be administered on the morning of one of the two experimental days by a RN or the physician investigator.

Placebo

Intervention Type: DRUG

Two matching tablets of placebo will be administered on the morning of one of the two experimental days by an RN or the physician investigator.

FHN; Mavoglurant-Placebo

Family History Negative (FHN) for alcoholism will be given a single dose of AFQ056 (200 mg) then placebo in two separate experimental study visits separated by 1 week. Drug and Placebo administered 2 hours prior to the MRI and other measures.

Group Type: EXPERIMENTAL

Mavoglurant (AFQ056)

Intervention Type: DRUG

Two 100mg tablets of Mavoglurant will be administered on the morning of one of the two experimental days by a RN or the physician investigator.

Placebo

Intervention Type: DRUG

Two matching tablets of placebo will be administered on the morning of one of the two experimental days by an RN or the physician investigator.

FHN; Placebo-Mavoglurant

Family History Negative (FHN) for alcoholism will be given a single dose of placebo then AFQ056 (200 mg) in two separate experimental study visits separated by 1 week. Drug and Placebo administered 2 hours prior to the MRI and other measures.

Group Type: EXPERIMENTAL

Mavoglurant (AFQ056)

Intervention Type: DRUG

Two 100mg tablets of Mavoglurant will be administered on the morning of one of the two experimental days by a RN or the physician investigator.

Placebo

Intervention Type: DRUG

Two matching tablets of placebo will be administered on the morning of one of the two experimental days by an RN or the physician investigator.

Interventions

Mavoglurant (AFQ056)

Two 100mg tablets of Mavoglurant will be administered on the morning of one of the two experimental days by a RN or the physician investigator.

Intervention Type: DRUG

Placebo

Two matching tablets of placebo will be administered on the morning of one of the two experimental days by an RN or the physician investigator.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ages 18-45 years
• Estimated full-scale IQ>70
• Individual can cooperate with all study procedures
• No history of neurological disorder (e.g., epilepsy)
• No major medical condition (e.g., cancer)
• No history of significant head trauma
• Stable medication treatment 6 weeks prior to study enrollment
• Negative urine drug and breathe alcohol test at time of MRI scan
• Negative urine pregnancy test at time of MRI scan
• No MR contra-indications (e.g., in-body metal implant, severe claustrophobia)
• No contra-indications to study drug

Exclusion Criteria

• A diagnosis of any psychotic disorder, or current mood or anxiety disorders under DSM-V, using the SCID-V-RV psychiatric interview
• A current diagnosis of: a) Alcohol use disorder, if severe (AUD, mild or moderate OK if no craving, tolerance, and withdrawal 3 months prior to interview) b) Substance use disorder
• Report of psychotic disorder in a 1º relative
• Auditory or visual impairment that interferes with test-taking
• Prenatal exposure to alcohol plus currently meeting criteria for features of fetal alcohol syndrome
• Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English > grade 1
• Intellectual Disability (Full Scale IQ<70)
• Traumatic brain injury with loss of consciousness > 30 minutes or concussion in last 30 days
• Presence or history of neurosurgery or any neurologic illness that may affect brain physiology (e.g., epilepsy, Multiple Sclerosis), including focal brain lesion seen on structural MRI (all structural scans are read by a board certified radiologist)
• A current major medical condition (e.g. cancer, heart failure)
• Current pregnancy (all females will be tested with urine screens on the day of MRI)
• Women not on an effective form of birth control/contraception or abstinent during time of study visits to prevent exposure of the investigational drug to suspected fetus
• Current substance use with the exception of marijuana (THC), provided last use of THC was 24+ hours before visit (All participants will receive a urine screen for the presence of marijuana, cocaine, opiates and a breath screen to detect the presence of alcohol)
• Inability to comprehend the consent form appropriately
• Inability to cooperate with study procedures
• Other specific fMRI exclusions include metal devices, clips or fragments in body (orbital xray performed if needed)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Godfrey Pearlson

Professor of Psychiatry and of Neuroscience

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Godfrey D Pearlson, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Hartford Hospital

Hartford, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Godfrey D Pearlson, MD

Role: CONTACT

godfrey.pearlson@hhchealth.org

203-737-3416

Facility Contacts

Godfrey D Pearlson, MD

Role: primary

godfrey.pearlson@hhchealth.org

203-737-3416

Other Identifiers

2P50AA012870-21

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000032425

Identifier Type: OTHER

Identifier Source: secondary_id

HHC-2021-0006

Identifier Type: -

Identifier Source: org_study_id