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: 8288790
• 负责人: Charles A Czeisler
• 金额: $ 31.43万
• 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/8288790
• 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

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 proposal 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.

褪黑激素是松果体在夜间产生的一种激素。其发布时间受到控制 通过昼夜节律计时系统。它的计时可以通过暴露在光下来抑制或重置 从眼睛到视交叉上核（主生物钟）的多突触通路。 据报道，外源性褪黑激素补充剂对人类有两种作用： （促进睡眠）和计时生物（重置昼夜节律阶段），从而影响两者 相互作用调节睡眠和觉醒的神经生物学系统。褪黑素补充剂有 据报道，它是治疗昼夜节律睡眠障碍的有效方法，包括轮班工作 许多盲人都患有睡眠障碍、时差反应、睡眠时相延迟综合症和睡眠障碍 个人。然而，在最近的一项荟萃​​分析中，绝大多数这些报告被排除在外 因为它们不是随机对照试验。结论是褪黑素不 对于与时差和轮班工作相关的睡眠问题有效。鉴于普遍存在的情况， 一般情况下，不受控制地使用非处方褪黑激素来治疗睡眠问题 人群中，褪黑激素的随机对照试验对于评估治疗效果至关重要 短暂性失眠。 目前的提案将分阶段测试褪黑激素的生物钟和促进睡眠的作用 失眠的先进模型。受试者将在试验前服用褪黑激素或安慰剂 预定的睡眠时间提前几个小时，模拟向东旅行。在下面 这些条件、低睡眠压力和生物钟的时间安排使睡眠特别困难 难的。之后我们将测量睡眠和昼夜节律控制的多种生理节律。 褪黑激素或安慰剂给药，并使用精确的分析方法来确定褪黑激素或安慰剂的影响 褪黑激素对睡眠和人体昼夜节律系统的影响。这项研究将提供重要 有关褪黑激素作用机制的信息对于褪黑激素的使用至关重要 作为昼夜节律睡眠障碍的治疗。