Efficacy of melatonin treatment in a phase advance model of insomnia

褪黑素治疗失眠阶段进展模型的疗效

• 批准号: 8111938
• 负责人: Charles A Czeisler
• 金额: $ 31.75万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111938
• 关键词: Accidents; Address; Affect; Agonist; Arousal; Biological Clocks; Body Temperature; Circadian Rhythm Sleep Disorders; Circadian Rhythms; Delayed Sleep Phase Syndrome; Development; Disease; Dose; Evidence based treatment; Exposure to; Eye; Food Supplements; Gastrointestinal Diseases; General Population; Health; Hormones; Hour; Human; Hydrocortisone; Individual; Jet Lag Syndrome; Laboratories; Lead; Light; Maintenance; Measures; Melatonin; Meta-Analysis; Methods; Modeling; North America; Outcome; Pathway interactions; Performance; Phase; Phase response curves; Physiological; Pineal gland; Placebos; Plasma; Primary Insomnia; Process; Property; Randomized Controlled Trials; Reporting; Research Personnel; Safety; Schedule; Simulate; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleeplessness; Supplementation; System; Testing; Time; Transient Insomnia; Travel; United States; Visually Impaired Persons; Wakefulness; alertness; awake; base; circadian pacemaker; cost; effective therapy; experience; heart disease risk; improved; pressure; shift work; sleep onset; suprachiasmatic nucleus; systematic review; treatment duration

DESCRIPTION (provided by investigator): Melatonin is a hormone produced by the pineal gland at night. The timing of its release is controlled by the circadian timing system. Its timing can be suppressed or reset by exposure to light through a multisynaptic pathway from the eye through the suprachiasmatic nucleus, the master circadian clock. Exogenous melatonin supplementation has been reported to act in two ways in humans: as a soporific (sleep-promoting) and a chronobiotic (to reset circadian phase), thus affecting both of the neurobiologic systems that interact to regulate sleep and wakefulness. Melatonin supplements have been reported to be an effective treatment for circadian rhythm sleep disorders, including shift work dyssomnia, jet-lag, delayed sleep phase syndrome, and sleep disruption suffered by many blind individuals. However, in a recent meta-analysis, the vast majority of these reports were excluded because they were not randomized controlled trials. The conclusion was that melatonin is not efficacious for sleep complaints associated with jetlag and shift work. In view of the widespread, uncontrolled, over-the-counter use of melatonin for treating sleep complaints in the general population, a randomized controlled trial of melatonin is essential to evaluate efficacy in treatment of transient insomnia. The current application will test the chronobiotic and sleep promoting effects of melatonin in a phase advance model of insomnia. Subjects will be administered either melatonin or placebo before a scheduled sleep episode which is advanced by several hours, simulating eastward travel. Under these conditions, low sleep pressure and the timing of the circadian clock make sleep particularly difficult. We will measure sleep and multiple physiologic rhythms controlled by the circadian after melatonin or placebo administration, and use precise analytic methods to determine the impact of melatonin on sleep and the human circadian timing system. This study will provide important information regarding the mechanism of action of melatonin that will be critical for the use of melatonin as a treatment for circadian rhythm sleep disorders. PUBLIC HEALTH RELEVANCE: Melatonin supplements have been reported to be an effective treatment for circadian rhythm sleep disorders, including shift work dyssomnia, jet-lag, delayed sleep phase syndrome, and sleep disruption suffered by many blind individuals. However, the mechanism(s) by which melatonin affects the timing of sleep are not well- understood. This study will provide important information regarding the mechanism of action of melatonin that will be critical for the use of melatonin as a treatment for circadian rhythm sleep disorders.

描述（由研究者提供）：褪黑激素是松果体在夜间产生的一种激素。其释放时间由昼夜节律系统控制。通过从眼睛到视交叉上核（主生物钟）的多突触通路暴露在光线下，可以抑制或重置其时间。据报道，外源性褪黑激素补充剂对人类有两种作用：作为催眠剂（促进睡眠）和计时生物剂（重置昼夜节律阶段），从而影响相互作用调节睡眠和觉醒的神经生物系统。据报道，褪黑激素补充剂可以有效治疗昼夜节律睡眠障碍，包括轮班工作睡眠障碍、时差反应、睡眠时相延迟综合征以及许多盲人所遭受的睡眠中断。然而，在最近的荟萃分析中，绝大多数报告被排除在外，因为它们不是随机对照试验。结论是褪黑激素对于与时差和轮班工作相关的睡眠问题无效。鉴于广泛、不受控制的非处方褪黑激素用于治疗普通人群的睡眠问题，褪黑激素的随机对照试验对于评估短暂性失眠的治疗效果至关重要。目前的应用将在失眠的阶段提前模型中测试褪黑激素的生物钟和睡眠促进作用。受试者将在预定的睡眠时间之前服用褪黑激素或安慰剂，该睡眠时间提前几个小时，模拟向东旅行。在这些情况下，低睡眠压力和生物钟的时间安排使睡眠变得特别困难。我们将测量褪黑素或安慰剂给药后的睡眠和昼夜节律控制的多种生理节律，并使用精确的分析方法来确定褪黑素对睡眠和人体昼夜节律计时系统的影响。这项研究将提供有关褪黑激素作用机制的重要信息，这对于使用褪黑激素治疗昼夜节律睡眠障碍至关重要。公共健康相关性：据报道，褪黑激素补充剂可有效治疗昼夜节律睡眠障碍，包括轮班工作睡眠障碍、时差反应、睡眠时相延迟综合征以及许多盲人所遭受的睡眠中断。然而，褪黑激素影响睡眠时间的机制尚不清楚。这项研究将提供有关褪黑激素作用机制的重要信息，这对于使用褪黑激素治疗昼夜节律睡眠障碍至关重要。