Efficacy of melatonin treatment in a phase advance model of insomnia

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。其释放的时间由昼夜节律计时系统控制。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，它的时间可以被抑制或重置。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：作为催眠剂（促进睡眠）和生物钟（重置昼夜节律），从而影响相互作用以调节睡眠和觉醒的神经生物系统。据报道，褪黑激素补充剂是一种有效的治疗昼夜节律睡眠障碍，包括轮班工作障碍，时差反应，睡眠相位延迟综合征，和许多盲人遭受的睡眠中断。然而，在最近的荟萃分析中，这些报告中的绝大多数被排除，因为它们不是随机对照试验。结论是褪黑激素对与时差和轮班工作有关的睡眠投诉无效。鉴于褪黑激素在一般人群中广泛、不受控制、非处方使用以治疗睡眠问题，褪黑激素的随机对照试验对于评估治疗短暂性失眠的疗效至关重要。本申请将测试褪黑激素在失眠的相位推进模型中的生物钟效应和睡眠促进效应。受试者将在提前几个小时的预定睡眠事件之前接受褪黑激素或安慰剂给药，模拟向东旅行。在这种情况下，低睡眠压力和生物钟的定时使睡眠特别困难。我们将测量褪黑激素或安慰剂给药后由昼夜节律控制的睡眠和多种生理节律，并使用精确的分析方法来确定褪黑激素对睡眠和人类昼夜节律计时系统的影响。这项研究将提供有关褪黑激素的作用机制的重要信息，这将是至关重要的使用褪黑激素作为昼夜节律睡眠障碍的治疗。公共卫生相关性：据报道，褪黑激素补充剂是一种有效的治疗昼夜节律睡眠障碍，包括轮班工作障碍，时差反应，睡眠相位延迟综合征，和许多盲人遭受的睡眠中断。然而，褪黑激素影响睡眠时间的机制还不清楚。这项研究将提供有关褪黑激素的作用机制的重要信息，这将是至关重要的使用褪黑激素作为昼夜节律睡眠障碍的治疗。

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.