Exogenous Melatonin in Intensive Care Unit Chronodisruption: Randomized Controled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Total sleep time
研究概览
简要总结
To this day, a small number of studies have evaluated the effect of melatonin on the modifications of the characteristics of sleep in critical care units, with mostly a small studied population. However, no study has been realized on a large population, nor has it evaluated the association between genetic factors and response to treatment (melatonin), hence the originality of our study. In our study we hypothesized that systematic melatonin usage in ICU can ameliorate the total sleep time and the fragmentation index and can decrease the confusion related to sleep deprivation.
详细描述
- Rationale:
1.1. Sleep and the circadian rhythm: Sleep is usually considered to be a time of rest and recovery from the stress of daily life. It also plays a crucial role in the normal immune and endocrine systems. Studies showed that there is a link between sleep duration and a large variety of health issues, including obesity, diabetes mellitus, hypertension and depression. Furthermore, sleep deprivation has been linked to immunosuppression as well as alterations in normal wound healing, thermoregulation and upper airway muscles (leading to a blunted response to hypercapnia and hypoxia).
Sleep is divided into 2 cycles: non-REM (NREM) sleep and REM sleep. NREM sleep is divided into 4 more stages (1, 2, 3 and 4). REM sleep is characterized by the presence of rapid ocular movements, and is commonly known as the phase during which dreams occur. Most individuals progress through the various stages, starting from NREM stage 1, to finally reach REM sleep. Usually, each sleep cycle lasts 90 minutes , with an average of 4-5 cycles per night.
During sleep, various hormonal changes occur, which shows the importance of sleep in the normal functioning of the body. Growth hormone and cortisol are released during sleep, and melatonin levels markedly increased at sleep initiation, with a decrease right before waking up. Circadian rhythms are normal fluctuations of the biological function, and are part of an endogenous 24 hour clock situation in the supra-chiasmatic nucleus (SCN) of the anterior hypothalamus, responsible for controlling the day/night variations of physiological and behavioral functions of the organism. These wake/sleep cycles are usually divided into an average of 8 hours of nocturnal sleep and 16 hours of wakefulness in humans.
Circadian rhythms make cyclic environmental changes easier to adapt to, and influence a number of behaviors and physiological parameters. This is due to a genetic molecular clock which is present in most nucleated cells. This clock is composed of a group of transcription factors and regulators of transcription factors which exerce a retro-control over one another. Thus, protein of the molecular clock can have very important effects on the transcriptional activity and the metabolism, leading, directly or indirectly, to a variation of 50% of the total gene pool.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo, double blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients or their parents who have signed an informed consent allowing us to exploit and analyse their clinical, biological and pharmacological data (see Appendix 1)
- •Patients staying more than 48 hours in ICU (acute ICU confusion occurs in the 48-72h following admission)
- •Drugs affecting sleep architecture (co-variables):
- •Opiates: increase N2, decrease REM
- •NSAIDs: reduce sleep efficacy, increase arousal
- •Beta blockers: insomnia, REM sleep disappearance
- •Corticosteroids (varies according to half life and dose): REM sleep disappearance, induce awakening, stimulant effect
- •Haloperidol: increases sleep efficacy, increases N2 duration
- •Respiratory assistance: ventilated patients v/s non ventilated patients (co-variables)
- •Patients presenting with delirium or sleep disorders at admission will not be excluded, but a note will be taken on the baseline case report form (CRF)
排除标准
- •Patients less than 18 years old
- •Patients with central neurological disease: post traumatic patients, Parkinson disease, patients presenting with CVA, patients with neurodegenerative diseases, etc.
- •Patients taking drugs capable of altering or inducing delirium:
- •Atypical antipsychotics (olanzapine, risperidone, etc.), which increase sleep efficacy, total sleep time, and NREM sleep, and reduce prevalence of ICU psychosis
- •BZD-like drugs (zolpidem, zopiclone) which induce delirium
- •Melatonin allergy
- •Any disorders capable of altering oral melatonin absorption (e.g. intestinal occlusion)
- •Predicted ICU stay of less than 24 hours (e.g. post surgical monitoring)
研究组 & 干预措施
Melatonin
Patients will be administered melatonin 5 mg at a fixed time every day during their ICU stay (from day of admission till day of discharge from ICU)
干预措施: Melatonin 5 mg (Drug)
Placebo
Patients will be administered a placebo pill that is identical in shape and color to the melatonin pill, at a fixed time every day during their ICU stay
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Total sleep time
时间窗: 14 days or ICU discharge, whichever came first
total time spent sleeping in ICU (in minutes)
次要结局
- REM sleep latency(14 days or ICU discharge, whichever came first)
- Fragmentation index(14 days or ICU discharge, whichever came first)
- Incidence of delirium in ICU(14 days or ICU discharge, whichever came first)
- Sleep efficacy(14 days or ICU discharge, whichever came first)
- Degree of agitation of patients(14 days or ICU discharge, whichever came first)
- Gene polymorphism(14 days or ICU discharge, whichever came first)
- Sleep latency(14 days or ICU discharge, whichever came first)