Suvorexant for Alcoholism
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
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.
12345Eligibility 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
+15 more
Trial 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
Participant Groups
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.
3Treatment groups
Active Control
Placebo Group
Group I: Non treatmentActive Control1 Intervention
Healthy Volunteers will receive two PET scans and one MRI session without any treatment.
Group II: SuvorexantActive Control1 Intervention
AUD subjects randomized to receive Suvorexant (20 mg po) for up to 4 weeks during inpatient treatment.
Group III: PlaceboPlacebo Group1 Intervention
AUD subjects randomized to receive placebo for up to 4 weeks during inpatient treatment.
Suvorexant is already approved in United States, Australia, 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 Australia 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Lead Sponsor
References
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]Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers.
Extended release naltrexone for alcohol use disorders: quasi-experimental effects on mortality and subsequent detoxification episodes. [2022]Utilization of extended release naltrexone (XRN) for alcohol use disorders (AUDs) in the U.S. Veterans Health Administration (VHA) has been limited, perhaps due to high cost, lack of established superiority over less expensive alternatives including oral naltrexone, and related formulary restrictions. Despite these barriers, pockets of higher utilization exist in VHA, allowing for the quasi-experimental examination of the effects of XRN on 1-year mortality and number of subsequent detoxification episodes among patients with high rates of psychiatric comorbidities and previous psychosocial and pharmacological addiction treatment.
Single-Dose Interaction Study of the Arginine Vasopressin Type 1B Receptor Antagonist ABT-436 and Alcohol in Moderate Alcohol Drinkers. [2016]ABT-436, a potent and selective arginine vasopressin (AVP) type 1B receptor (V1B ) antagonist, has previously demonstrated basal hypothalamic-pituitary-adrenal (HPA) axis attenuation in man. A V1B antagonist is hypothesized as an alcohol-dependent treatment based on the role of the V1B receptor in stress regulation and the finding that stress is a trigger for relapse in alcoholics. A V1B antagonist has shown favorable effects in rat models of alcohol dependence. A single-dose clinical study was conducted to assess the potential for pharmacokinetic or pharmacodynamic interaction between ABT-436 and alcohol.
mGlu2 mechanism-based interventions to treat alcohol relapse. [2022]Recently we identified a deficiency in metabotropic glutamate receptor 2 (mGlu2) function in the corticoaccumbal pathway, as a common pathological mechanism underlying alcohol-seeking and relapse behavior. Based on this mechanism, we hypothesized that mGlu2/3 agonists and mGlu2 positive allosteric modulators (PAMs) may be effective in reducing relapse-like behavior. Two mGlu2/3 agonists, LY379268 and LY354740 (a structural analog of LY379268 six-fold more potent in activating mGlu2 over mGluR3), were tested in a well-established rat model of relapse, the alcohol deprivation effect (ADE) with repeated deprivation phases. Since these agonists do not readily discriminate between contributions of mGlu2 and mGluR3, we also tested LY487379, a highly specific PAM that potentiates the effect of glutamate on the mGlu2 with less specificity on other mGlu receptor subtypes. Both LY379268 and LY354740 significantly and dose-dependently reduced the expression of the ADE. No significant changes in water intake, body weight and locomotor activity were observed. Importantly, repeated administration of mGlu2/3 agonist did not lead to tolerance development. mGlu2 PAM LY487379 treatment significantly reduced expression of the ADE in both male and female rats. Combination treatment of mGlu2/3 agonist and PAM had similar effect on relapse-like drinking to that seen in mGlu2/3 agonist treatment alone. Together with other preclinical data showing that PAMs can reduce alcohol-seeking behavior we conclude that mGlu2 PAMs should be considered for clinical trials in alcohol-dependent patients.
A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. [2019]The opioid antagonist, naltrexone, is reported, in single centre studies, to improve the clinical outcome of individuals with alcohol dependence participating in outpatient psychosocial programmes. This is the first multicentre controlled study to evaluate the efficacy and safety of naltrexone as adjunctive treatment for alcohol dependence or abuse. Patients who met criteria for alcohol dependence (n = 169) or alcohol abuse (n = 6) were randomly assigned to receive double-blind oral naltrexone 50 mg daily (n = 90) or placebo (n = 85) for 12 weeks as an adjunct to psychosocial treatment. The primary efficacy variable was time to first episode of heavy drinking; secondary efficacy assessments included time to first drink, alcohol consumption, craving, and changes in the serum biological markers gamma-glutamyl transferase (GGT), and aspartate and alanine aminotransferases. Compliance was assessed by tablet counts and, in the naltrexone-treated group, by measurement of urinary concentrations of 6-ss-naltrexol. Forty-nine (58%) patients randomized to placebo and 53 (59%) randomized to naltrexone did not complete the study. In intention-to-treat analyses, there was no difference between groups on measures of drinking. The median reduction from baseline of serum GGT (P: