An Alpha2-adrenoceptor Agonist to Reduce Locus Coeruleus Activity During Sleep in Adults With Insomnia Disorder: a Pilot Randomised Placebo-controlled Cross-over Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Electrographic (EEG) signatures
研究概览
简要总结
This research project aims to better understand the neurobiological mechanistic underpinnings of insomnia disorder. The main question is whether cortical hyperarousal in individuals with insomnia disorder, measured by electroencephalograhic (EEG) infraslow oscillation coupling of sigma power during non-rapid eye movement (NREM) sleep and theta power during rapid eye movement (REM) sleep, is related to locus coeruleus activity.
详细描述
This trial is a double-blinded, placebo-controlled, randomised controlled cross over trial of dexmedetomidine or placebo in adults with insomnia disorder. Participants will be recruited using social media, bulletin boards and patient referrals from the Woolcock Institute of Medical Research clinics. Participants will be asked to complete an online pre-screening webpage (RedCap) to check for eligibility, and provided with the Participant Information Sheet (PIS) and asked for contact details for an in-person screening visit. The participants will have the study explained in detail during the screening visit followed by written informed consent. The participant will then undergo a medical screening for diagnosis of insomnia disorder and the medical officer will sign the consent form. Thereafter, the participant will complete baseline questionnaires and be randomised to either dexmedetomidine or placebo for the 2 sleep laboratory visits. Participants will then be instructed to maintain their regular sleep-wake patterns for seven days before the first sleep laboratory visit (Visit 1). During Visit 1, participants will undergo a number of assessments (pre-sleep locus coeruleus activity measured using pupillometry, electroencephalography (EEG), functional near-infrared spectroscopy (fNIRS) before and during sleep and questionnaires about subjective hyperarousal. Participants will receive either dexmedetomidine or placebo. Following Visit 1, participants will have a 14-day washout, before Visit 2, which will repeat the procedures of Visit 1, but participants will receive the alternate condition (placebo or dexmedetomidine). The study will be coordinated from the Woolcock Institute of Medical Research, Sydney, Macquarie University, NSW, 2113, Australia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All trial staff (except one unblinded researcher) and participants will be blinded to the intervention and control medication. We will use identical containers and labels except a patient identification code. The order of treatments will be secured in a password-protected data management system and known by the unblinded researcher.
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of insomnia disorder (DSM-5-TR)
- •Insomnia severity index (ISI) score ≥15
- •Able to provide informed consent
- •Fluent English literacy
排除标准
- •Medically diagnosis of sleep disordered breathing (i.e. sleep apnea) or sleep or circadian disorder other than insomnia
- •Uncontrolled psychiatric disorders
- •High dependence on medical care
- •History of, or current suicide ideation (Patient Health Questionnaire (PHQ-9) questionnaire)
- •Pregnancy or actively trying to conceive, or lactating
- •Shiftwork - defined as work outside of business hours (before 8am or after 6pm) conducted at least once per week
- •Travel across time zones of over 2 h time difference in the past week
- •Contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with clinical study procedures
- •Concomitant use of medicines that are inhibitors, or moderate to strong inducers, of CYP3A4; regular use of hypnotics and other medications that can cause additive sedation or psychostimulants or non-amphetamine psychostimulants within 14 days of starting the clinical trial
- •Ongoing use of THC- or CBD-containing products; dependence or any other drug or alcohol dependence
- •Allergy to lactose
研究组 & 干预措施
Placebo
Matching placebo tablet taken during the sleep laboratory visit only
干预措施: Placebo (Drug)
Dexmedetomidine
A 96 µg dexmedetomidine tablet taken during the sleep laboratory visit only
干预措施: Dexmedetomidine (Drug)
结局指标
主要结局
Electrographic (EEG) signatures
时间窗: Baseline and 14 days
Electrographic (EEG) infraslow oscillations (\~50 sec) of sigma power and sleep spindle coupling during non-rapid eye movement (NREM) sleep and theta power during rapid eye movement (REM) sleep.
次要结局
- Sleep Fragmentation(Baseline and 14 days)
- EEG power(Baseline and 14 days)
- Neurovascular activity (fNIRS)(Baseline and 14 days)
- Cardiopulmonary Coupling (CPC)(Baseline and 14 days)
- Pupillometry(Baseline and 14 days)
- Subjective hyperarousal(Baseline and 14 days)
- Subjective sleep quality(Baseline and 14 days)
研究者
Christopher Gordon
Research Leader
Woolcock Institute of Medical Research