A Placebo-controlled, Double -Blind Randomised Trial of Suvorexant in the Management Comorbid Sleep Disorder and Alcohol Dependence
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Sleep measure
研究概览
简要总结
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.
详细描述
Study Procedures Baseline On Day 1, prior to commencement of treatment baseline data will be collected on demographics, ISI questionnaire plus 2 short questions 1) how many hours sleep has the participant had for the past week; 2) how would the participant rate their sleep quality in the past week. The investigators will also determine previous drug use history, physical examination, urine drug screen and measures of alcohol dependence severity, psychological and social functioning (ATOPv7).
Treatment Period Treatment will begin immediately after collection of Baseline data. Suvorexant will not be given if breath alcohol concentration is above zero. Both groups will be treated using the St Vincent's Hospital standard protocol for management of alcohol withdrawal, in which benzodiazepines are provided as required according to the symptoms listed in the Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). That is, if the CIWA-Ar score is > 10 then benzodiazepines (BZD) are administered. Note, BZD will not be given for management of insomnia. Physicians involved in patient care, nurses and participants will be blinded to treatment assignment. Participants will be monitored for signs of adverse events (i.e. distress, significant alcohol withdrawal, and adverse response to suvorexant) approximately 4 hourly for the first 24 - 48 hrs of residential stay and then according to clinical assessment. All clinical observations will be made by a suitably qualified and experienced medical professional. Where any adverse events are observed, monitoring will be increased to meet clinical needs and treatment discontinued if required. Alcohol withdrawal severity will be assessed using the Clinical Institute Withdrawal Assessment - Alcohol revised (CIWA-Ar).
Note, during in-patient assessment there will be no consumption of alcohol (7-10 days). Upon release to outpatients the investigators will advise participants not to consume alcohol and will provide follow-up support to help maintain abstinence. If patients resume heavy drinking and are deemed to have relapsed i.e. daily alcohol consumption greater than 5 standard drinks each day, the investigators will tell them to cease the medication and they will be withdrawn from the study. Data collected to this point will be included in the study.
Follow-up Treatment Subsequent follow-up would occur weekly for 4 weeks post inpatient treatment and then every 4 weeks to week 25. Patients will continue the same dose of Suvorexant/placebo for the duration of the follow-up period. At the end of the 25 week trial patients will continue to receive treatment as usual. If they wish to continue to receive suvorexant they can get a prescription from their GP (suvorexant has been added to the pharmaceutical benefits scheme).
Data Collection Baseline
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Patients will be treated from pre-packaged blinded treatment schedules.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
- •Less than 18 years of age
- •Over 75 years of age.
研究组 & 干预措施
Treatment group
Patients (n=64): 20mg tablets of suvorexant nocte daily for six months
干预措施: Suvorexant 20 mg (Drug)
Placebo group
Placebo control group: Patients (n=64): 1 placebo tablet nocte daily for six months in addition to treatment as usual
干预措施: placebo (Other)
结局指标
主要结局
Sleep measure
时间窗: 7-10 days
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 {%}).
次要结局
- Relapse measure(25 weeks)
- Sleep measure(25 weeks)
- Abstinence measure(25 weeks)
- Urine drug screen(25 weeks)
- Sleepiness measure(25 weeks)
- Liver function measure(25 weeks)
- Sleep quality: Pittsburgh Sleep Quality Index (PSQI)(25 weeks)
- Craving measure(25 weeks)