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

October 6, 2025 updated by: Godfrey Pearlson, Yale University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Hartford Hospital
        • Contact:
        • Principal Investigator:
          • Godfrey D Pearlson, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: 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.
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.
Experimental: 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.
Drug: 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.
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.
Experimental: 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.
Drug: 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.
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.
Experimental: 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.
Drug: 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.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Nucleus accumbens (Nacc)/Ventral striatum (VS) BOLD activation during A1 phase in FHP on study medication vs. placebo
Time Frame: Mavoglurant and Placebo administration are 1 week apart
Changes in NAcc/VS BOLD (Blood-oxygen-level-dependent) activation during the A1 loss anticipation prospect phase of the MRI Monetary Incentive Delay task in FHP while on mavoglurant compared to placebo
Mavoglurant and Placebo administration are 1 week apart
BOLD activation to alcohol vs. non-alcohol stimuli during ACR task alcohol versus non-alcohol stimuli
Time Frame: Mavoglurant and Placebo administration are 1 week apart
Changes in BOLD response in FHP to alcohol versus non-alcohol stimuli in several brain clusters containing MFC, caudate, parahippocampal gyrus, temporal cortex and cerebellum, when administered mavoglurant compared to placebo
Mavoglurant and Placebo administration are 1 week apart

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Dynamic Causal Modeling (DCM)-determined relationships between nucleus accumbens (NAcc) and -medial PFC BOLD signal during MSDM task
Time Frame: Mavoglurant and Placebo administration are 1 week apart
Dynamic Causal Modeling (DCM)-determined relationships between nucleus accumbens (NAcc) and -medial PFC BOLD signal during MSDM fMRI task in FHP while on mavoglurant compared to placebo
Mavoglurant and Placebo administration are 1 week apart
Regional differences in BOLD signal
Time Frame: Mavoglurant and Placebo administration are 1 week apart
Impairment of top down inhibitory control and related cortical activation of the executive control network in FHP while on mavoglurant compared to placebo measured by regional differences in BOLD signaling
Mavoglurant and Placebo administration are 1 week apart

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Godfrey D Pearlson, MD, Yale University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 17, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 5, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 10, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2022

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 9, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HHC-2021-0006
  • 2P50AA012870-21 (U.S. NIH Grant/Contract)
  • 2000032425 (Other Identifier: Yale IRB)

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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