Suvorexant for Alcoholism

Overseen By William W Stoops, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Kentucky

Must not be taking: Chronic condition medications

Disqualifiers: Severe SUD, Psychiatric diagnoses, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This research will translate findings from preclinical research and provide the initial clinical evidence that orexin antagonism reduces motivation for alcohol, as well as other alcohol-associated maladaptive behaviors in people with Alcohol Use Disorder. This study will also provide basic science information about the orexinergic mechanisms underlying the pharmacodynamic effects of alcohol in humans. As such, the outcomes will contribute to our understanding of the clinical neurobiology of Alcohol Use Disorder. Overall, the proposed work seeks to expand the scope of current clinical neuroscience research on alcohol addiction by focusing on orexin, which has strong preclinical evidence supporting its critical role in addiction but remains unstudied in humans.

Will I have to stop taking my current medications?

Yes, you must not be taking any prescribed medications for a chronic condition, except for birth control, to participate in this trial.

How does the drug Suvorexant differ from other treatments for alcoholism?

Suvorexant is unique because it is primarily used as a sleep aid, working by blocking orexin receptors in the brain, which are involved in wakefulness. This mechanism is different from other alcoholism treatments like naltrexone, which targets opioid receptors, or mGluR modulators, which affect glutamate receptors. ^{1 2 3 4 5}

Research Team

William W Stoops, Ph.D.

Principal Investigator

University of Kentucky

Eligibility Criteria

This trial is for English-speaking adults aged 21-55 with Alcohol Use Disorder (AUD) who are not pregnant, breastfeeding, or have sleep apnea. Participants must be healthy overall, not dependent on alcohol or other substances, and not seeking treatment. They should have had at least one binge drinking episode recently but can't be taking chronic medication except birth control.

Inclusion Criteria

No indication of sleep apnea on the STOP-Bang questionnaire (score of 5 or greater)

Able to speak and read English

Birthing individuals using an effective form of birth control and not pregnant or breast feeding

Exclusion Criteria

Not currently physiologically dependent on any substances

I am not currently seeking any cancer treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Inpatient Treatment

Participants are admitted to the inpatient unit and treated daily with oral suvorexant or placebo. Various tasks and measurements are conducted.

2.5 weeks

Daily inpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Suvorexant

Trial Overview The study is testing the effects of a drug called suvorexant on people with AUD to see if it reduces their desire for alcohol and related negative behaviors. It aims to understand how orexin (a brain chemical linked to addiction) affects alcohol's influence on humans.

Participant Groups

Group I: Suvorexant Dose 2 Experimental Treatment 2 Interventions

Subjects will be treated daily with oral suvorexant (20 mg).

Group II: Suvorexant Dose 1 Experimental Treatment 2 Interventions

Subjects will be treated daily with oral suvorexant (10 mg).

Group III: Placebo Placebo Group 2 Interventions

Subjects will be treated daily with an oral placebo.

Suvorexant is already approved in United States, Japan for the following indications:

Approved in United States as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Approved in Japan as Belsomra for:

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Who Is Running the Clinical Trial?

University of Kentucky

Lead Sponsor

Trials

198

Recruited

224,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

GET 73, a novel mGluR5 negative allosteric modulator, was found to be safe and well-tolerated in a Phase I study involving 80 healthy male volunteers, with no serious adverse events reported.

The study demonstrated a dose-related increase in plasma drug concentration, indicating that GET 73 is pharmacokinetically active and supports further investigation for treating neuropsychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers. Haass-Koffler, CL., Goodyear, K., Long, VM., et al.[2018]

In a rat model of alcohol relapse, mGlu2/3 agonists significantly reduced relapse-like behavior without causing tolerance, suggesting their potential as effective treatments for alcohol dependence.

The mGlu2 positive allosteric modulator (PAM) LY487379 also effectively decreased relapse behavior in both male and female rats, indicating that mGlu2 PAMs could be promising candidates for clinical trials in treating alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mGlu2 mechanism-based interventions to treat alcohol relapse. Vengeliene, V., Spanagel, R.[2022]

Patients with alcohol use disorders (AUDs) who received extended release naltrexone (XRN) had a significantly lower 1-year mortality rate compared to those who did not receive XRN, with an odds ratio of 0.30, indicating a strong protective effect.

Among patients with a history of detoxification, those treated with XRN experienced an average of 0.80 fewer detoxification episodes and also had lower mortality rates, suggesting that XRN may be particularly beneficial for individuals with complex psychiatric needs and a history of addiction treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended release naltrexone for alcohol use disorders: quasi-experimental effects on mortality and subsequent detoxification episodes. Harris, AH., Bowe, T., Del Re, AC., et al.[2022]

In a study involving 20 moderate alcohol drinkers, ABT-436, a V1B receptor antagonist, did not interact with alcohol in terms of blood levels or effects, indicating it can be safely used without exacerbating alcohol's negative impacts.

ABT-436 effectively reduced serum cortisol levels, demonstrating its potential to attenuate stress responses without being affected by alcohol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Interaction Study of the Arginine Vasopressin Type 1B Receptor Antagonist ABT-436 and Alcohol in Moderate Alcohol Drinkers. Katz, DA., Locke, C., Liu, W., et al.[2016]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

mGlu2 mechanism-based interventions to treat alcohol relapse. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Extended release naltrexone for alcohol use disorders: quasi-experimental effects on mortality and subsequent detoxification episodes. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Single-Dose Interaction Study of the Arginine Vasopressin Type 1B Receptor Antagonist ABT-436 and Alcohol in Moderate Alcohol Drinkers. [2016]

5. 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]