Suvorexant for Alcoholism

Overseen By Michele-Vera I Yonga, C.R.N.P.

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

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 3 to 4 weeks for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week.

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.

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

Nora Volkow, M.D.

Principal Investigator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Eligibility Criteria

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

I am between 18 and 75 years old.

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

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

Treatment Details

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.

Participant Groups

Group I: 2nd [11C]NNC-112 Active Control 1 Intervention

Follow-up \[11C\]NNC-112 scan to measure dopamine D1receptors in AUD participants at end of Suvorexant/Placebo dosing during inpatient stay.

Group II: 2nd [11C]raclopride Active Control 1 Intervention

Follow-up \[11C\]raclopride scan to measure striatal dopamine release in AUD participants at end of Suvorexant/Placebo dosing during inpatient stay.

Group III: Baseline [11C]raclopride Placebo Group 1 Intervention

Baseline \[11C\]raclopride scan to measure striatal dopamine release in all participants.

Group IV: Baseline [11C]NNC-112 Placebo Group 1 Intervention

Baseline \[11C\]NNC-112 PET scan to measure dopamine D1receptors in all participants.

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+

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]

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 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]

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. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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]