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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug suvorexant (also known as Belsomra or MK-4305) can reduce the desire to drink and other alcohol-related behaviors in people with Alcohol Use Disorder (AUD). The study will test two different doses of suvorexant and compare them to a placebo (a sugar pill with no active drug). It aims to deepen understanding of how alcohol affects the brain and find new ways to treat addiction. Individuals who have had at least one episode of binge drinking in the last 30 days and meet the criteria for moderate or severe AUD might find this trial suitable. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering a unique opportunity to contribute to groundbreaking addiction research.

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.

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

Research has shown that suvorexant, the treatment being tested in this trial, affects sleep and behaviors related to alcohol use. In earlier studies, suvorexant improved sleep in people with Alzheimer's disease, suggesting it might be safe as a sleep aid. Another study found that suvorexant reduced alcohol cravings and improved both physical and mental health in some individuals.

Importantly, the FDA has already approved suvorexant for treating insomnia, indicating its safety. FDA approval means thorough testing for human use, although for different conditions than Alcohol Use Disorder. While this trial remains in the early stages, existing research on suvorexant's use in other conditions provides some reassurance about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for alcoholism involve behavioral therapy and medications like naltrexone, acamprosate, or disulfiram, which work by reducing cravings or causing unpleasant reactions to alcohol. But Suvorexant works differently, targeting the brain's orexin system, which is involved in regulating wakefulness and potentially cravings. This unique mechanism could offer a fresh approach by directly influencing the neurological pathways associated with addiction. Researchers are excited about Suvorexant because it might not only help manage cravings but also improve sleep patterns, a common issue for those with alcoholism, offering a dual benefit not seen with current medications.

What evidence suggests that suvorexant might be an effective treatment for Alcohol Use Disorder?

Research suggests that suvorexant, a medication that blocks certain signals in the brain, might help reduce alcohol cravings and improve health in people with Alcohol Use Disorder. Some studies have found that suvorexant can help people sleep better and lower stress-related triggers that lead to drinking. In animal studies, it prevented returning to alcohol use when stressed. While these findings are promising, most evidence comes from early research or studies on other conditions, like sleep problems. This trial will evaluate the effectiveness of suvorexant at different doses, as well as a placebo, to confirm its effectiveness specifically for reducing alcohol use in humans. ^{1 2 3 6 7}

Who Is on the Research Team?

William W Stoops, Ph.D.

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11063611/

The dual orexin receptor antagonist suvorexant in alcohol ... We demonstrate improvements in alcohol cravings, physical and psychological health, and sleep outcomes with treatment. These data support ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02750306

NCT02750306 | Safety and Efficacy of Suvorexant (MK- ... This study aims to examine the safety and efficacy of suvorexant (MK-4305) to improve sleep in individuals with Alzheimer's disease (AD).

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/ccr3.8740

The dual orexin receptor antagonist suvorexant in alcohol ... We demonstrate improvements in alcohol cravings, physical and psychological health, and sleep outcomes with treatment. These data support ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9813433/

Alternative use of suvorexant (Belsomra®) for the prevention ... Furthermore, 5 mg/kg SUV prevented the stress-induced reinstatement of alcohol-seeking behavior in dependent rats only. These results underscore ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006899318304190

A sleeping giant: Suvorexant for the treatment of alcohol ... Suvorexant may address alcohol-induced sleep disruptions, which may in turn help reduce or prevent relapse.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06655883

NCT06655883 | A Study of Suvorexant (MK-4305) for the ... Participants receive 10 mg of suvorexant for the first three nights, increased to 20 mg of suvorexant nightly thereafter at the investigator's discretion, for ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2020/204569s006lbl.pdf

Belsomra - accessdata.fda.gov In an abuse liability study conducted in recreational polydrug users (n=36), suvorexant (40, 80 and 150 mg) produced similar effects as zolpidem (15, 30 mg) on ...