Melatonin Entrainment of Elderly Blind Free-runners

老年盲人自由跑步者褪黑激素的诱导作用

• 批准号: 6543177
• 负责人: ALFRED J LEWY
• 金额: $ 37.31万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6543177
• 关键词: bioperiodicity; blindness; chronotherapy; circadian rhythms; clinical research; dosage; hormone therapy; human old age (65+); human subject; longitudinal human study; melatonin; quality of life; sensory disorder chemotherapy; sleep; wakefulness

DESCRIPTION (provided by applicant): In our just completed project, we have shown that nightly oral administration of 10 mg melatonin can entrain (synchronize) free-running circadian rhythms in eight of nine younger blind people to the 24.0-hour day, resulting in improved nighttime sleep and daytime alertness. The one person who did not entrain had the longest pre-treatment free-running period (24.9 h). In addition, we have shown that 10 mg of melatonin has a direct soporific action when given to blind subjects when their free-running circadian rhythms are inverted. Most recently, we have found that the dose can be "stepped down" to 0.5 mg in three out of three of these people. We have further found that they could also be entrained to a de novo 0.5 mg dose (their longest free-running period was 24.4 h). The pre-treatment period appears to predict the likelihood of entrainment to melatonin and the steady-state phase of entrainment, which is consistent with several important principles established in animal studies. Therefore, our projects are of both clinical and scientific importance. There are approximately 200,000 totally blind people in the U.S. About 50 percent of these people have free-running circadian rhythms. Many of these people are elderly. The goal of this project will be to determine the efficacy of melatonin treatment at three doses (0.5 mg, 10 mg and 20 mg), with the prediction that the 0.5 mg dose will work only in people with relatively short periods (<24.5 h). In treatment failures with the 0.5 mg dose, we will test the efficacy of higher doses. Blind subjects who successfully entrain with melatonin will be followed for one year to assess the long-term benefits and risks of melatonin administration. It is particularly important to study the elderly blind, because - compared to younger blind people - they may be more susceptible to side effects of melatonin and they may respond differently to melatonin treatment. Among the many basic science questions that we will be addressing is the effect of age on circadian period. The study of blind people provides an opportunity to understand the physiology of the circadian system in humans unperturbed by the light/dark cycle.

描述（由申请人提供）：在我们刚刚完成的项目中，我们已经证明，每晚口服10 mg褪黑激素可以使9名年轻盲人中的8名的自由运行的昼夜节律保持（同步）到24.0小时，从而改善夜间睡眠和白天警觉性。一个人谁没有夹带有最长的治疗前自由运行时间（24.9小时）。此外，我们已经证明，当盲人的自由运行的昼夜节律被颠倒时，10毫克的褪黑激素具有直接的催眠作用。最近，我们发现这些人中有三人的剂量可以“降低”到0.5毫克。我们进一步发现，它们也可以被重新携带至0.5 mg剂量（它们的最长自由运行期为24.4 h）。预处理期似乎可以预测褪黑激素夹带的可能性和夹带的稳态阶段，这与动物研究中确立的几个重要原则一致。因此，我们的项目具有临床和科学的重要性。在美国大约有20万完全失明的人，其中大约50%的人有自由运行的昼夜节律。这些人中有许多是老年人。该项目的目标是确定三种剂量（0.5 mg，10 mg和20 mg）褪黑激素治疗的疗效，预测0.5 mg剂量仅适用于相对较短时间（<24.5小时）的人。在0.5 mg剂量治疗失败的情况下，我们将测试更高剂量的疗效。成功服用褪黑激素的盲人受试者将被随访一年，以评估褪黑激素给药的长期益处和风险。研究老年盲人尤其重要，因为与年轻盲人相比，他们可能更容易受到褪黑激素副作用的影响，并且他们对褪黑激素治疗的反应可能不同。在我们将要讨论的许多基础科学问题中，年龄对昼夜节律周期的影响是一个问题。对盲人的研究提供了一个机会，可以了解不受光/暗周期干扰的人类昼夜节律系统的生理学。