Mavoglurant for Alcohol Use Disorder

Recruiting at 1 trial location

Overseen By Thomas Liss

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

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)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 2-3 weeks

63 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to find out about the effects of a drug called mavoglurant on alcohol consumption.

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.

How does the drug Mavoglurant differ from other treatments for alcohol use disorder?

Mavoglurant is unique because it targets the metabotropic glutamate receptor subtype 5 (mGluR5), which is different from other treatments like naltrexone that focus on opioid receptors. This novel approach may offer a new way to address alcohol use disorder by affecting different brain pathways involved in addiction. ^{1 2 3 4 5}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. [2019]

2. Germany 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Enhanced Striatal Dopamine Release to Expectation of Alcohol: A Potential Risk Factor for Alcohol Use Disorder. [2021]

4. United Arab Emirates 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. [2023]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. [2019]