Suvorexant in the Management Comorbid Sleep Disorder and Alcohol Dependence

NCT03897062 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 49730
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Suvorexant (trade name Belsomra) is an orexin receptor antagonist that has TGA approval for the treatment of insomnia, characterised by difficulties with sleep onset and/or sleep maintenance. It may also have a role in addictions as the orexins play a critical role in drug addiction and reward-related behaviours. Orexins appear to be involved in both alcohol withdrawal and in alcohol seeking triggered by external cues (eg contexts or stressors) through both OX1 and OX2 receptor signalling. Chief investigator, Professor Lawrence was the first to demonstrate a role for endogenous orexin signaling in alcohol-seeking. Alcohol is known to effect the sleep of healthy and alcohol dependent individuals with effects on daytime sleepiness, physiological functions during sleep, and the development of sleep disorders. There are various estimates of the co-occurrence of insomnia and alcohol use disorder ranging from 36-72%. In alcohol dependent individuals sleep is disturbed both while drinking and for months of abstinence and abstinent sleep disturbance is predictive of relapse. This proposal aims to evaluate the use of suvorexant as a safe and effective pharmacotherapy to treat sleep disorders in alcohol dependent patients undergoing acute alcohol withdrawal and thereafter for six months. The study will also examine the effectiveness of suvorexant in reducing craving for alcohol and promoting duration of abstinence. This will be the first double blind controlled trial of suvorexant in the management of the alcohol withdrawal syndrome and maintenance of abstinence post withdrawal.

Conditions

Insomnia; Alcohol Use Disorder

Keywords

suvorexant; insomnia; alcohol use disorder; craving; withdrawal

Outcome Measures

Primary Outcomes (1)

• Sleep measure

  Change in polysomnography sleep efficiency measure from baseline and at end of inpatient stay. Portable Polysomnography is multichannel recording of the electrophysiological markers of sleep. Polysomnography (PSG) records brain activity, eye movements and muscle tone to identify stages of sleep. Sleep efficiency measure is number of minutes of sleep divided by the number of minutes in bed {%}).

  7-10 days

Secondary Outcomes (8)

• Sleep measure

  25 weeks

• Sleep quality: Pittsburgh Sleep Quality Index (PSQI)

  25 weeks

• Sleepiness measure

  25 weeks

• Abstinence measure

  25 weeks

• Relapse measure

  25 weeks

Study Arms (2)

Treatment group

ACTIVE COMPARATOR

Patients (n=64): 20mg tablets of suvorexant nocte daily for six months

Drug: Suvorexant 20 mg

Placebo group

PLACEBO COMPARATOR

Placebo control group: Patients (n=64): 1 placebo tablet nocte daily for six months in addition to treatment as usual

Other: placebo

Interventions

Suvorexant 20 mg DRUG

Placebo controlled double blind suvorexant vs placebo

Treatment group

placebo OTHER

Placebo controlled double blind suvorexant vs placebo

Placebo group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 18 years of age and not more than 75 years of age
• DSM-5 diagnosis of insomnia
• Alcohol dependent (SCID-5)
• Willing to comply with treatment and follow-up requirements of study
• Able to give informed consent

You may not qualify if:

• Consumes less than 6 standard drinks per day.
• Not alcohol dependent (SCID-5)
• Unstable major psychiatric disorder e.g. active psychosis, significant PTSD.
• Currently taking medication having major interaction with suvorexant
• Pregnant (urine βHCG positive) or not using adequate contraception.
• Breast feeding.
• Severe hepatic impairment (Liver enzyme levels \>five times normal level)
• Severe renal impairment (urine creatinine clearance \< 30ml/h)
• Severe medical disorder e.g. epilepsy, cardiovascular disorder
• Participating in another pharmacotherapy trial e.g. lorcaserin
• Highly dependent on medical care.
• Driver of any vehicle (car or commercial vehicle)
• Inability to take oral medication.
• No consent to participate in the study
• Known sensitivity to suvorexant.

Sponsors & Collaborators

• The Florey Institute of Neuroscience and Mental Health: lead
• St Vincent's Hospital Melbourne: collaborator
• Melbourne Health: collaborator

Study Sites (1)

St Vincent's Hospital

Melbourne, Victoria, 3065, Australia

Location

Related Publications (5)

• Walker LC, Lawrence AJ. The Role of Orexins/Hypocretins in Alcohol Use and Abuse. Curr Top Behav Neurosci. 2017;33:221-246. doi: 10.1007/7854_2016_55.

  PMID: 27909991 BACKGROUND

• Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B. The orexin system regulates alcohol-seeking in rats. Br J Pharmacol. 2006 Jul;148(6):752-9. doi: 10.1038/sj.bjp.0706789. Epub 2006 Jun 5.

  PMID: 16751790 BACKGROUND

• von der Goltz C, Koopmann A, Dinter C, Richter A, Grosshans M, Fink T, Wiedemann K, Kiefer F. Involvement of orexin in the regulation of stress, depression and reward in alcohol dependence. Horm Behav. 2011 Nov;60(5):644-50. doi: 10.1016/j.yhbeh.2011.08.017. Epub 2011 Sep 16.

  PMID: 21945150 BACKGROUND

• Brower KJ. Insomnia, alcoholism and relapse. Sleep Med Rev. 2003 Dec;7(6):523-39. doi: 10.1016/s1087-0792(03)90005-0.

  PMID: 15018094 BACKGROUND

• Roehrs T, Roth T. Sleep, sleepiness, and alcohol use. Alcohol Res Health. 2001;25(2):101-9.

  PMID: 11584549 BACKGROUND

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders; Alcoholism

Interventions

suvorexant

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Andrew Lawrence

  Florey Institute of Neuroscience & Mental Health

  PRINCIPAL INVESTIGATOR

• Yvonne Bonomo

  St Vincent's Hospital Melbourne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Patients will be treated from pre-packaged blinded treatment schedules.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A placebo-controlled, double-blind randomised trial

Study Record Dates

• First Submitted: March 26, 2019
• First Posted: April 1, 2019
• Study Start: August 26, 2019
• Primary Completion: July 31, 2022
• Study Completion: July 31, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)