Mavoglurant for Alcohol Use Disorder

Recruiting at 1 trial location

Overseen By Thomas Liss

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Yale University

Must not be taking: Psychoactive drugs

Disqualifiers: Substance use disorder, Psychotic disorders, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2-3 weeks

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how mavoglurant, a medication, affects alcohol consumption in people with Alcohol Use Disorder (AUD). Participants will receive either mavoglurant or a placebo (a harmless pill with no active drug) to compare the effects. Those diagnosed with moderate or severe AUD and who regularly consume a high amount of alcohol weekly might be a good fit for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 does mention that individuals on a stable dose of an antidepressant for at least 2 months can participate. Regular use of other psychoactive drugs is not allowed.

Is there any evidence suggesting that mavoglurant is likely to be safe for humans?

Research has shown that mavoglurant has been tested in various studies for its effects on alcohol and drug use. One study found that it reduced alcohol and cocaine use in individuals with long-term cocaine use disorder, suggesting potential benefits for alcohol use as well.

Regarding safety, other studies have examined mavoglurant's interaction with alcohol, aiding researchers in assessing its safety when taken with alcohol. Although detailed safety results are not yet available, previous human testing indicates it is considered safe enough for further study.

As this is an early-stage trial, it is designed to closely monitor participants' responses to the drug. Safety remains a top priority, and any side effects will be carefully observed. For those considering joining a trial with mavoglurant, this information provides insight into its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcohol use disorder?

Unlike the standard treatments for alcohol use disorder, which often include medications like naltrexone, acamprosate, or disulfiram, mavoglurant offers a different approach by targeting the mGluR5 receptor in the brain. This unique mechanism could potentially modify the brain's response to alcohol, diminishing cravings and reducing consumption. Researchers are particularly excited about mavoglurant's potential to provide benefits with just a single dose, offering a convenient and effective option for managing alcohol use disorder.

What evidence suggests that mavoglurant might be an effective treatment for alcohol use disorder?

Research has shown that mavoglurant could be a promising treatment for reducing substance use. It blocks a part of the brain called mGluR5, which is linked to addiction and mood problems. One study found that mavoglurant had a very high chance (≥99.0%) of reducing cocaine use. Although limited data exists on its effects on alcohol use disorder, its mechanism in the brain suggests it might help reduce alcohol cravings and consumption. This trial will evaluate mavoglurant's potential for alcohol use disorder. Early animal studies also suggest it can improve decision-making in subjects exposed to alcohol. ^{1 5 6 7 8}

Who Is on the Research Team?

Suchitra Krishnan, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for heavy drinkers aged 21-50 who can read English and meet criteria for moderate or severe alcohol use disorder. Men must consume 30-70 drinks weekly, women 20-65. Excluded are those seeking treatment recently, with substance disorders (except mild cannabis/tobacco), positive drug screens, serious mental/medical conditions, high liver enzymes or creatinine levels, pregnant/nursing women, and non-users of birth control.

Inclusion Criteria

You can read and understand English at a 6th grade level or higher.

You have been diagnosed with moderate or severe alcohol use disorder according to the DSM-V guidelines.

I am between 21 and 50 years old.

Exclusion Criteria

Meet current DSM-V criteria for substance use disorder, except for tobacco use disorder or mild cannabis use disorder

Clinically significant abnormalities in screening laboratories, including aspartate aminotransferase (AST) >1.5 times ULN; alanine aminotransferase (ALT) > 1.5 times ULN; total bilirubin >1.5 times ULN; serum creatinine >2.0 times ULN

Neurological trauma or disease, delirium or hallucinations, or clinically significant or unstable medical conditions, including uncontrolled hypertension or diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic diseases, which in the opinion of the study physician and PI, may put the patient at risk because of participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two lab sessions with a 5-8 day washout period in between, receiving either mavoglurant or placebo in a double-blind, placebo-controlled design

2-3 weeks

2 lab sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up appointments

5 weeks

1-week and 1-month follow-up appointments (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Mavoglurant
• Placebo

Trial Overview The study tests the effects of mavoglurant on alcohol craving and consumption in heavy drinkers compared to a placebo. Participants will not know if they're receiving the actual drug or a dummy pill (placebo). The goal is to see if mavoglurant helps reduce the desire to drink and overall alcohol intake.

How Is the Trial Designed?

Group I: Placebo 1st / Mavoglurant 2nd Experimental Treatment 1 Intervention

Participants randomized to the Placebo 1st Arm will take a matching placebo in the morning, prior to their 1st lab session. Then after a 5-8 day washout period, participants will have their 2nd lab session where they will take a single dose of 200mg mavoglurant in the morning, prior to their 2nd lab session.

Group II: Mavoglurant 1st / Placebo 2nd Experimental Treatment 1 Intervention

Participants randomized to the Mavoglurant 1st Arm will take a single dose of 200mg mavoglurant in the morning, prior to their 1st lab session. Then after a 5-8 day washout period, participants will have their 2nd lab session where they will take a matching placebo in the morning prior to the 2nd lab session.

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

Naltrexone is a moderately effective treatment for alcohol dependence, acting as an opioid receptor antagonist, and its efficacy is supported by various clinical studies.

Emerging research on naltrexone pharmacogenetics may help identify which patients are more likely to respond to the treatment based on their genetic makeup, paving the way for more personalized approaches in managing alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. Ray, LA., Chin, PF., Miotto, K.[2019]

In a multicentre controlled study involving 175 patients, naltrexone (50 mg daily) was found to significantly reduce alcohol consumption and craving in those who adhered to the treatment, compared to a placebo group.

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 adjunctive treatment for alcohol dependence when combined with psychosocial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Chick, J., Anton, R., Checinski, K., et al.[2019]

GET 73 is safe and well-tolerated when taken with alcohol, showing no serious adverse events in a study involving alcohol-dependent individuals.

While GET 73 did not reduce alcohol craving or consumption in the lab, it did enhance the sedative effects of alcohol, suggesting further research is needed to explore its potential benefits in longer-term outpatient settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An inpatient human laboratory study assessing the safety and tolerability, pharmacokinetics, and biobehavioral effect of GET 73 when co-administered with alcohol in individuals with alcohol use disorder. Haass-Koffler, CL., Perciballi, R., Magill, M., et al.[2023]

The paper highlights the complexity of developing pharmacological treatments for alcohol abuse and dependence due to the disease's heterogeneous nature and its impact on multiple neurotransmitter systems, which complicates effective treatment strategies.

Currently, the FDA has approved three main medications for alcoholism—disulfiram, naltrexone, and acamprosate—while also exploring new patents targeting various neurotransmitter systems to improve treatment outcomes, including the potential for personalized medicine through pharmacogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction to the special issue "Pharmacotherapies for the treatment of alcohol abuse and dependence" and a summary of patents targeting other neurotransmitter systems. Bell, RL., Franklin, KM., Hauser, SR., et al.[2023]

In a study involving 128 PET scans of 63 participants consuming alcohol and 65 consuming a placebo, alcohol consumption was found to significantly increase dopamine release in the ventral striatum compared to placebo, indicating its strong effect on the brain's reward system.

Participants with a family history of alcohol use disorder (AUD) showed a unique response pattern, where those who had placebo first exhibited lower dopamine binding and less difference in dopamine release between alcohol and placebo, suggesting that their expectation of alcohol may heighten their risk for developing AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder. Kegeles, LS., Horga, G., Ghazzaoui, R., 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. reporter.nih.gov reporter.nih.gov/search/UfJ5ODrVdk6T1oqPIG2j8Q/project-details/9352672

Project Details Influence of Mavoglurant on Alcohol Craving and Drinking in ... Harnessing telemedicine to improve alcohol use disorder outcomes in primary care patients.

4. synapse.patsnap.com synapse.patsnap.com/article/stalicla-starts-us-phase-3-ddi-study-of-stp7-mavoglurant-for-cocaine-use-disorder

STALICLA starts U.S. Phase 3 DDI study of STP7 ... The mGluR5 receptor has been linked to addiction, mood disorders, and neurodevelopmental disorders like Fragile X and autism spectrum disorder.

5. researchgate.net researchgate.net/publication/390436671_Mavoglurant_reduces_cocaine_use_in_patients_with_cocaine_use_disorder_in_a_phase_2_clinical_trial

Mavoglurant reduces cocaine use in patients with ... The posterior probability of mavoglurant reducing cocaine use at the end of treatment was ≥99.0% for a treatment difference <0 and ≥36.6% for a treatment ...

6. reporter.nih.gov reporter.nih.gov/project-details/10482357

Medication Development for the Treatment of Alcohol Use ... As required by the FDA, preliminary data for our CMMs show a significant reduction of alcohol consumption in two mammalian species. We have patents covering ...

7. researchgate.net researchgate.net/publication/266678244_AFQ056mavoglurant_a_novel_clinically_effective_mGluR5_antagonist_Identification_SAR_and_pharmacological_characterization

AFQ056/mavoglurant, a novel clinically effective mGluR5 ... In this small and short trial, mavoglurant reduced cocaine and alcohol use in patients with chronic cocaine use disorder. View. Show abstract.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03327792

NCT03327792 | Mavoglurant in Alcohol Drinking A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved ...