Suvorexant for Alcoholism

Overseen By Nora D Volkow Adler, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Must not be taking: Antipsychotics, Antidepressants, Opioids, others

Disqualifiers: Severe mental illness, Severe depression, Severe hepatic impairment, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Suvorexant, a medication typically used for sleep issues, affects brain dopamine receptors in individuals with alcohol use disorder (AUD) and healthy volunteers. Dopamine, a brain chemical linked to addiction, is under investigation to see if Suvorexant can alter its activity in those with AUD. The study involves two groups: participants with AUD will either take Suvorexant or receive a placebo (a non-active pill), and all will undergo brain scans and other tests. Ideal candidates for the AUD group are those seeking treatment for AUD, with a history of heavy drinking and sleep problems, while healthy volunteers should not have any significant psychiatric or substance use disorders. As a Phase 1, Phase 2 trial, this study focuses on understanding how Suvorexant works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

Participants with AUD must stop using certain medications like stimulants, antipsychotics, and strong CYP3A inhibitors before joining the trial. Healthy volunteers should not be on medications that affect brain function, like antidepressants or opioids, for at least two months before the study.

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

Research shows that suvorexant, a drug typically used for sleep problems, is being studied for its potential benefits in treating alcohol use disorder (AUD). Studies have found that suvorexant is generally well-tolerated, improving sleep and reducing alcohol cravings. This suggests it might be beneficial for those with AUD.

Regarding safety, suvorexant has been tested in various situations. For instance, it has been used to help individuals with Alzheimer's disease sleep better without major safety issues. Additionally, in a study with recreational drug users, suvorexant produced effects similar to another sleep drug, zolpidem, without serious problems.

Suvorexant is already FDA-approved for sleep issues, indicating it has passed strict safety checks for that use. However, its use for AUD remains under investigation. Participants in clinical trials contribute to understanding how safe and effective suvorexant is for this new purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for alcoholism, which often include medications like naltrexone, acamprosate, and disulfiram that target cravings and withdrawal symptoms, Suvorexant offers a unique approach by acting on the brain's orexin system. This system plays a crucial role in regulating wakefulness and arousal, which can influence alcohol-seeking behavior. Researchers are excited about Suvorexant because it could potentially reduce the urge to drink by promoting better sleep and reducing anxiety, giving it a distinct advantage over existing therapies.

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

Research has shown that Suvorexant, a drug primarily used for sleep issues, might benefit individuals with alcohol use disorder (AUD). In this trial, some participants will receive Suvorexant, which studies have found can reduce alcohol cravings and enhance both physical and mental health. Early results also indicate it aids sleep, crucial because sleep problems can trigger relapse. In animal studies, Suvorexant prevented stress-induced alcohol-seeking behavior. These findings suggest it could be a promising treatment for AUD. ^{1 2 3 4 6}

Who Is on the Research Team?

Nora D Volkow Adler, M.D.

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Are You a Good Fit for This Trial?

This trial is for individuals aged 18 to 75 who are seeking treatment for Alcohol Use Disorder (AUD) and healthy volunteers. Participants with AUD will undergo detoxification and receive standard treatments, while healthy subjects will be monitored without the need for detox.

Inclusion Criteria

Participants must have the ability to understand and the willingness to sign a written informed consent document

All participants must have stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

Have had previous radiation exposure that would exceed NIH annual research limits

My body weight is over 400 lbs.

Pregnant or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Detoxification

Participants with AUD undergo alcohol detoxification and receive normal treatment for AUD

3-4 weeks

Inpatient stay

Treatment

Participants receive either Suvorexant or placebo for up to 4 weeks during inpatient treatment

4 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including imaging scans and cognitive tests

4 weeks

Multiple visits for imaging and tests

What Are the Treatments Tested in This Trial?

Interventions

• Suvorexant

Trial Overview The study tests Suvorexant's effects on dopamine receptors in the brain among those with AUD and healthy people. It involves taking Suvorexant or a placebo daily, movement tracking, blood tests, brain imaging scans (PET and MRI), cognitive assessments, and sleep studies.

How Is the Trial Designed?

Group I: Non treatment Active Control 1 Intervention

Healthy Volunteers will receive two PET scans and one MRI session without any treatment.

Group II: Suvorexant Active Control 1 Intervention

AUD subjects randomized to receive Suvorexant (20 mg po) for up to 28 days during inpatient treatment.

Group III: Placebo Placebo Group 1 Intervention

AUD subjects randomized to receive placebo for up to 28 days during inpatient treatment.

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?

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Lead Sponsor

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

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 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 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]

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]

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. 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 ...

4. 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 ...

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. 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 ...