A Novel Inhaled Formulation of Melatonin to Treat Adults With Insomnia Disorder: a Randomised Open-Label Crossover Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Time to maximum Melatonin concentration
研究概览
简要总结
The goal of this clinical trial is to explore the potential benefits of an inhaled version of melatonin compared to oral melatonin tablets on adults with insomnia. The main question the trial aims to answer: is the time required for inhaled melatonin to reach peak concentration in the blood and then be eliminated from body different to that of oral melatonin tablets, in adults with insomnia?
5 participants will:
- Visit the research institute for a screening visit and for a daytime visit to take a melatonin treatment then provide blood samples over the course of 8 hours for each study drug treatment (3 visits in total)
- Take 100 μg of inhaled melatonin (2 inhaler puffs) once
- Take a 4 mg of oral melatonin (2 tablets) once
详细描述
This is a randomised open-label cross-over study of an inhaled formulation of melatonin (100 µg) versus oral melatonin tablets (4 mg) in adults with insomnia. The experiments performed for this trial will examine the effects of inhaled and oral drug delivery on the uptake and clearance of inhaled and oral melatonin.
To be enrolled in the trial, participants are required to complete an online pre-screening survey. Eligible participants will be directed to a separate webpage where they will be invited to review and download the Participant Information Sheet (PIS) and asked to provide their contact details and consent for a follow up call/email from the research team to book in a screening visit. At the screening visit, the study team will explain the study to each participant and provide the opportunity to ask any questions. The study team will also ensure participants have had ample time prior to the visit to read and understand the PIS. The consent form will be signed by both the participant and a medical officer and participants. Once participants have joined the efficacy study, they will be randomised into their first treatment group; inhaled melatonin (100 µg) or oral melatonin tablets (4 mg).
Participants will attend the laboratory for a daytime visit where they take the treatment once in the morning then remain at the laboratory over an approximately 8-hour period, providing blood samples every fifteen minutes during the first hour then hourly until 8 hours have passed since treatment. Participants will also be asked to rate their sleepiness on the Karolinska Sleepiness Scale each time blood is collected. There will be a 1 week washout period between treatments.
The study will recruit primarily through social media advertisements. 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
- Treatment
- 盲法
- None
盲法说明
As this trial is open-label, all study staff and participants will not be blinded.
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of insomnia disorder as defined by the DSM-5 (difficulty initiating or maintaining sleep or waking up too early for at least 3 nights per week, for at least 3 months, with adequate opportunity and circumstances for sleep and at least one daytime impairment related to the sleep difficulty) and a score ≥15 on the ISI.
- •History of subjective sleep onset latency (sSOL) ≥30 minutes on at least 3 nights per week in the previous 4 weeks.
- •Able to provide informed electronic consent.
- •Fluent English literacy.
- •Adults aged 55+ years old.
排除标准
- •People highly dependent on medical care as determined by a medical officer.
- •Untreated moderate-severe sleep apnoea as diagnosed using in-home wrist oximetry (oxygen desaturation index>15, ongoing effectively treated sleep apnoea with insomnia will be allowed).
- •Circadian disorders, narcolepsy, severe restless legs syndrome, and REM sleep behaviour disorder or uncontrolled psychiatric disorders.
- •History of attempted suicide or current suicide ideation (indicated by a score >0 on Q9 of the Patient Health Questionnaire-9) at pre-screening.
- •Objective cognitive decline measured by scoring ≤26 on the Montreal Cognitive Assessment (MoCA)
- •Regular shift work, jet lag or trans-meridian travel (over 2h time difference) in the past week before randomisation.
- •Pregnancy or lactation. Female participants of childbearing potential with a fertile sexual partner must have a negative serum pregnancy test result at the screening visit. Women will be advised to use contraception for the duration of the study.
- •Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with clinical study procedures.
- •Currently participating in or has participated in a research study of an investigational agent or device within 4 weeks of enrolment.
- •Ongoing use of anti-psychotic medication, bosentan, efavirenz, etravirine, modafinil, rifampin, carbamazepine or illicit stimulants.
- •Regular use of hypnotics (including melatonin, valerian, kava, benzodiazepines and Z-drugs), and other medications that can cause additive sedation (e.g. sedating antihistamines, tricyclic antidepressants, antipsychotics) within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
- •Regular use of psychostimulants (e.g., dexamfetamine, lisdexamfetamine, methylphenidate) or non-amphetamine psychostimulants (e.g., armodafinil, modafinil, atomoxetine) within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
- •Use of antidepressant medications for treatment of low mood for less than one year or dose changes (escalation or tapering) or change in antidepressant medications within the past year.
- •Regular use opioids within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
- •Ongoing use of THC- or CBD-containing products within 14 days prior to the start of the trial.
- •Dependence or any other drug or alcohol dependence within the past two years (alcohol to be limited to no more than 2 standard drinks per day during trial period).
- •Regular use of drugs that are CYP1A2 inhibitors (e.g. amiodarone, cimetidine, ciprofloxacin, fluvoxamine) or CYP1A2 inducers (e.g. carbamazepine, phenobarbital, rifampin, tobacco).
研究组 & 干预措施
Inhaled Melatonin Arm
100 µg daily of inhaled melatonin delivered by pressurized metered dose inhaler for two weeks before habitual bedtime.
干预措施: Inhaled Melatonin (100 μg) (Drug)
Oral Melatonin Arm
4 mg daily of orally delivered melatonin tablets for two weeks before habitual bedtime.
干预措施: Oral Melatonin (4 mg) (Drug)
结局指标
主要结局
Time to maximum Melatonin concentration
时间窗: 0-8 hours post-treatment.
Time to peak concentration (Tmax) of blood-based melatonin, analysed by melatonin ELISA.
次要结局
- Melatonin area under the curve(0-8 hours post-treatment.)
- Maximum blood-based melatonin concentration(0-8 hours post-treatment.)
- Melatonin half-life(0-8 hours post-treatment.)
- Daytime sleepiness(Collected at t0 then every fifteen minutes during the first hour post-treatment, then once hourly until 8 hours post-treatment.)
研究者
Hui Xin Ong
Chief Scientific Officer, Principal Investigator, Senior Research Fellow
Woolcock Institute of Medical Research