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

NCT05203965 | Recruiting Early Phase 1 DMC FDA Drug

• 3 other identifiers: HHC-2021-00062P50AA012870-212000032425
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Familial Alcoholism Vulnerability

Outcome Measures

Primary Outcomes (2)

• Change in Nucleus accumbens (Nacc)/Ventral striatum (VS) BOLD activation during A1 phase in FHP on study medication vs. placebo

  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

  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 Outcomes (2)

• Dynamic Causal Modeling (DCM)-determined relationships between nucleus accumbens (NAcc) and -medial PFC BOLD signal during MSDM task

  Mavoglurant and Placebo administration are 1 week apart

• Regional differences in BOLD signal

  Mavoglurant and Placebo administration are 1 week apart

Study Arms (4)

FHP; Mavoglurant-Placebo

EXPERIMENTAL

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); Drug: Placebo

FHP; Placebo-Mavoglurant

EXPERIMENTAL

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); Drug: Placebo

FHN; Mavoglurant-Placebo

EXPERIMENTAL

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); Drug: Placebo

FHN; Placebo-Mavoglurant

EXPERIMENTAL

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); Drug: Placebo

Interventions

Mavoglurant (AFQ056) 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.

FHN; Mavoglurant-Placebo; FHN; Placebo-Mavoglurant; FHP; Mavoglurant-Placebo; FHP; Placebo-Mavoglurant

Placebo 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; FHN; Placebo-Mavoglurant; FHP; Mavoglurant-Placebo; FHP; Placebo-Mavoglurant

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Hartford Hospital

Hartford, Connecticut, 06106, United States

RECRUITING

MeSH Terms

Interventions

mavoglurant

Study Officials

• Godfrey D Pearlson, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Godfrey D Pearlson, MD

CONTACT

203-737-3416; godfrey.pearlson@hhchealth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and of Neuroscience

Study Record Dates

• First Submitted: January 5, 2022
• First Posted: January 24, 2022
• Study Start: May 17, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: October 9, 2025

Record last verified: 2025-10

Locations

US (1)