Familial Alcoholism VulnerabilityEarly Phase 1NCT05203965
Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant
A Early Phase 1 study testing Mavoglurant (AFQ056) in people with Familial Alcoholism Vulnerability, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Familial Alcoholism Vulnerability
- What is being tested?
- Mavoglurant (AFQ056)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- 17 May 2022to 31 May 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Mavoglurant (AFQ056), Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Mavoglurant (AFQ056); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
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
Measured: Mavoglurant and Placebo administration are 1 week apart
Regional differences in BOLD signal
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
Measured: Mavoglurant and Placebo administration are 1 week apart
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2022
- Study start17 May 2022
- Primary completion31 May 2026
- Study completion31 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial Alcoholism VulnerabilityStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Godfrey Pearlson, Yale University
- Investigators
- Godfrey D Pearlson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05203965
- Sponsor's protocol ID
- HHC-2021-0006
- Other IDs
- 2P50AA012870-21, 2000032425
- Status last verified
- Aug 2026
- First submitted
- 5 Jan 2022
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant
- ClinicalTrials.gov ID
- NCT05203965
- Acronym / sponsor ID
- HHC-2021-0006
- Conditions
- Familial Alcoholism Vulnerability
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 17 May 2022 (actual)
- Primary completion
- 31 May 2026 (actual)
- Study completion
- 31 May 2026 (actual)
- First posted
- 24 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| FHP; Mavoglurant-Placebo | Experimental | Drug: Mavoglurant (AFQ056), Drug: PlaceboFamily 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. |
| FHP; Placebo-Mavoglurant | Experimental | Drug: Mavoglurant (AFQ056), Drug: PlaceboFamily 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. |
| FHN; Mavoglurant-Placebo | Experimental | Drug: Mavoglurant (AFQ056), Drug: PlaceboFamily 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. |
| FHN; Placebo-Mavoglurant | Experimental | Drug: Mavoglurant (AFQ056), Drug: PlaceboFamily 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | FHN; Mavoglurant-Placebo, FHN; Placebo-Mavoglurant, FHP; Mavoglurant-Placebo, FHP; Placebo-Mavoglurant |
| PlaceboTwo matching tablets of placebo will be administered on the morning of one of the two experimental days by an RN or the physician investigator. | Drug | FHN; Mavoglurant-Placebo, FHN; Placebo-Mavoglurant, FHP; Mavoglurant-Placebo, FHP; Placebo-Mavoglurant |
Primary outcome
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
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
2 secondary outcomes
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
Regional differences in BOLD signal
Time frame: Mavoglurant and Placebo administration are 1 week apart
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Godfrey D Pearlson, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Mavoglurant (AFQ056) in people with Familial Alcoholism Vulnerability, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.