Suvorexant for Alcoholism
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Kentucky
Must not be taking: Chronic condition medications
Disqualifiers: Severe SUD, Psychiatric diagnoses, others
Approved in 3 Jurisdictions
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.
12345Eligibility 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
+9 more
Exclusion Criteria
Not currently physiologically dependent on any substances
I am not currently seeking any cancer treatment.
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Suvorexant Dose 2Experimental Treatment2 Interventions
Subjects will be treated daily with oral suvorexant (20 mg).
Group II: Suvorexant Dose 1Experimental Treatment2 Interventions
Subjects will be treated daily with oral suvorexant (10 mg).
Group III: PlaceboPlacebo Group2 Interventions
Subjects will be treated daily with an oral placebo.
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:
Psychopharmacology of Addiction LaboratoryLexington, KY
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Who Is Running the Clinical Trial?
University of KentuckyLead Sponsor
National Institute on Alcohol Abuse and Alcoholism (NIAAA)Collaborator
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.
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.
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.
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: