Mavoglurant for Alcoholism

Overseen By Godfrey Pearlson, M.D

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Yale University

Must not be taking: Antidepressants, Antipsychotics

Disqualifiers: Psychotic disorder, Severe AUD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Mavoglurant (also known as AFQ-056 or STP-7) might clarify the brain's role in alcoholism risk. Participants will receive a single dose of the drug and a placebo (inactive substance) in different sessions to observe how each affects brain activity. The trial seeks volunteers with and without a family history of alcoholism, provided they have no major medical conditions or neurological disorders. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a unique opportunity to contribute to groundbreaking scientific discovery.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that your medication treatment is stable for 6 weeks before joining the study. This suggests you should not change your medications during this time.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mavoglurant has been tested for various conditions, including mental health disorders like Fragile X syndrome. Studies have found mavoglurant to be generally safe and well tolerated. In one study, it reduced cocaine and alcohol use in individuals with long-term cocaine addiction, and participants reported it was safe to take.

While these results are encouraging, this trial remains in the early stages. Limited information exists about its safety for this specific use. However, mavoglurant's use in other studies and conditions provides some initial confidence in its safety. Participants should discuss any concerns with their healthcare providers before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcoholism?

Researchers are excited about mavoglurant for alcoholism because it offers a fresh approach by targeting the mGluR5 receptor, a pathway not typically utilized by current alcohol addiction treatments. Most standard treatments, like naltrexone and acamprosate, focus on the opioid or glutamate systems in different ways. However, mavoglurant's unique action on the mGluR5 receptor could offer new hope for those who haven't responded to existing therapies. Additionally, its potential to influence brain activity related to alcohol cravings makes it a promising candidate for more effective management of alcoholism.

What evidence suggests that Mavoglurant might be an effective treatment for alcoholism?

Research shows that mavoglurant, a new drug tested in this trial, might help people reduce alcohol consumption. Participants will receive either mavoglurant or a placebo in different sequences. Studies have found that mavoglurant can decrease the desire to drink and the amount of alcohol consumed by individuals with substance use issues. One study found that mavoglurant helped people who use cocaine drink less alcohol and use less cocaine. This drug blocks certain parts of the brain, which might help control the urge to drink. Although more research is needed, early results are promising for those at risk of alcoholism. ^{1 2 6 7 8}

Who Is on the Research Team?

Godfrey D Pearlson, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-45 with an IQ over 70, who can follow study procedures and have no major neurological disorders, medical conditions like cancer, significant head trauma, or metal implants. Participants must test negative for drugs/alcohol and women must not be pregnant nor planning to become so during the trial.

Inclusion Criteria

Stable medication treatment 6 weeks prior to study enrollment

Negative urine drug and breathe alcohol test at time of MRI scan

I have no known allergies or reactions to the study medication.

Exclusion Criteria

I have not been diagnosed with a psychotic, mood, or anxiety disorder.

Other specific fMRI exclusions include metal devices, clips or fragments in body (orbital xray performed if needed)

I had a head injury with unconsciousness over 30 minutes or a recent concussion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Mavoglurant or placebo in a double-blind, randomized, counterbalanced manner, with two separate visits separated by 1 week.

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on changes in BOLD activation and brain function related to alcoholism vulnerability.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mavoglurant (AFQ056)
• Placebo

Trial Overview The study tests Mavoglurant's effects on alcoholism risk by comparing it against a placebo in a controlled environment. Each participant will receive both treatments at different times (200mg dose) without knowing which one they're getting first.

How Is the Trial Designed?

Group I: FHP; Placebo-Mavoglurant Experimental Treatment 2 Interventions

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 II: FHP; Mavoglurant-Placebo Experimental Treatment 2 Interventions

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 III: FHN; Placebo-Mavoglurant Experimental Treatment 2 Interventions

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 IV: FHN; Mavoglurant-Placebo Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

In a preclinical study with male Long Evans rats, the mixed mGlu4/mGlu7 agonist LSP2-9166 significantly reduced ethanol self-administration and motivation for ethanol, suggesting its potential as a treatment for alcohol addiction.

The study demonstrated that LSP2-9166 effectively decreased the reacquisition of ethanol self-administration after a period of abstinence, supporting the idea that targeting mGlu receptors could help prevent relapse in addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol consumption and relapse in rat. Lebourgeois, S., Vilpoux, C., Jeanblanc, J., et al.[2018]

The mu-opioid receptor antagonist CTOP significantly reduced alcohol consumption in both male and female AA rats over three days, indicating its potential as a treatment for alcohol use.

In contrast, the delta-opioid receptor antagonist ICI 174,864 had no effect on alcohol drinking in males and caused adverse effects, such as hind limb dysfunction, in many females, highlighting the safety concerns associated with targeting delta-opioid receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of mu-opioid receptors in alcohol drinking by alcohol-preferring AA rats. Hyytiä, P.[2019]

Low concentrations of ethanol (EtOH) significantly reduce NMDA receptor-mediated excitatory postsynaptic potentials (EPSPs) in the nucleus accumbens (NAcc) neurons, suggesting a mechanism by which EtOH may influence reward pathways associated with addiction.

The effects of EtOH on NMDA currents are dose-dependent and occur independently of opioid receptors, indicating that EtOH may modulate glutamate signaling both pre- and postsynaptically, which could contribute to its reinforcing properties in alcohol use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethanol inhibits glutamatergic neurotransmission in nucleus accumbens neurons by multiple mechanisms. Nie, Z., Madamba, SG., Siggins, GR.[2018]

The cyclized dipeptide glycyl-L-glutamine (c-GQ) significantly reduced ethanol consumption in both high-drinking (P) and low-drinking (Sprague-Dawley) rats, with an average decrease of 34.4% and 39.4% respectively after peripheral injections.

These results suggest that c-GQ has therapeutic potential for reducing alcohol intake, indicating its effectiveness across different drinking behaviors in rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyclo-glycyl-glutamine inhibits ethanol intake in P and Sprague-Dawley rats. Resch, GE., Simpson, CW.[2018]

The study found that the mGluR1 negative allosteric modulator JNJ-16259685 effectively reduced alcohol consumption in mice, indicating its potential as a treatment for alcohol use disorders.

The reduction in alcohol intake was linked to mGluR1-PLC signaling in the nucleus accumbens, and this effect depended on the presence of the Homer2 protein, highlighting a specific neuroanatomical and molecular mechanism involved in alcohol reinforcement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mGluR1 within the nucleus accumbens regulates alcohol intake in mice under limited-access conditions. Lum, EN., Campbell, RR., Rostock, C., et al.[2021]

Citations

1. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/92/NCT03327792/Prot_SAP_001.pdf

A Pilot Study on the Safety and Efficacy of Mavoglurant ... The purpose of this study is to evaluate interactions between a moderate dose of alcohol and a non-competitive antagonist of the metabotropic ...

2. reporter.nih.gov reporter.nih.gov/search/oeuu5d53-Um_uHhUUB5M7Q/project-details/11127633

Project Details Decision-making strategies in male and female alcohol-exposed mice will be determined and the ability of mavoglurant treatment to restore both MSDM strategies ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06136195

Influence of Mavoglurant on Alcohol Craving and Drinking ... This project will use a double-blind, placebo-controlled, within-subject design to examine mavoglurant effects on alcohol craving, drinking, and subjective ...

4. sciencemediacentre.es sciencemediacentre.es/en/drug-reduces-cocaine-and-alcohol-use-small-clinical-trial

Drug reduces cocaine and alcohol use in clinical trial An experimental drug called mavoglurant can reduce the consumption of both cocaine and alcohol in people with cocaine use disorder.

5. withpower.com withpower.com/trial/phase-2-alcoholism-2024-0fe6b

Mavoglurant for Alcohol Use Disorder Naltrexone also led to a greater reduction in serum GGT levels, indicating improved liver function, and raised no safety concerns, supporting its efficacy as an ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11513716/

The mGlu5 receptor negative allosteric modulator ... Mavoglurant has been tested in humans for several different conditions, including neuropsychiatric disorders, such as Fragile X syndrome ( ...

7. science.org science.org/doi/abs/10.1126/scitranslmed.adi4505

Mavoglurant reduces cocaine use in patients with ... In this small and short trial, mavoglurant reduced cocaine and alcohol use in patients with chronic cocaine use disorder.

8. medchemexpress.com medchemexpress.com/Mavoglurant.html?srsltid=AfmBOoqWNkbUmtPZqzksWwCfaGMu18002mIjigbcZAYhXK4HxTjGB_1e

Mavoglurant (AFQ056) | mGluR5 Antagonist Mavoglurant can be used for the research of Fragile X syndrome (FXS), and L ... SAFETY DATA SHEET (SDS). English - EN (392 KB) Français - FR (392 KB) ...