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: 8468010
• 负责人: Jeanne F Duffy
• 金额: $ 29.92万
• 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 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468010
• 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。其发布的时间受到控制 昼夜节律计时系统。它的计时可以通过暴露在光线中来抑制或重置 多突触通路从眼睛通过视交叉上核，主生物钟。 据报道，外源性褪黑激素补充剂在人类中以两种方式起作用： （促进睡眠）和时间生物素（重置昼夜节律），从而影响两个 神经生物系统相互作用来调节睡眠和觉醒。褪黑激素补充剂 据报道，它是一种有效的治疗昼夜节律睡眠障碍，包括轮班工作 许多盲人患有精神障碍、时差反应、睡眠期延迟综合征和睡眠中断， 个体然而，在最近的荟萃分析中，这些报告中的绝大多数被排除在外 因为它们不是随机对照试验。结论是褪黑激素 有效的睡眠投诉与时差和轮班工作。鉴于普遍存在的， 不受控制的，非处方使用褪黑激素治疗睡眠投诉， 人群中，褪黑激素的随机对照试验是必不可少的，以评估治疗效果 短暂性失眠 目前的提议将在一个阶段测试褪黑激素的生物钟和睡眠促进作用 失眠症的先进模型受试者将在治疗前施用褪黑激素或安慰剂。 提前几个小时的预定睡眠片段，模拟向东旅行。下 这些条件，低睡眠压力和生物钟的定时使睡眠特别 难我们将测量睡眠和多种生理节律控制的昼夜节律后， 褪黑激素或安慰剂给药，并使用精确的分析方法来确定 褪黑激素对睡眠和人体昼夜节律计时系统的影响。这项研究将提供重要的 关于褪黑激素作用机制的信息，这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方法。