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: 7110115
• 负责人: ALFRED J LEWY
• 金额: $ 36.86万
• 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 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7110115
• 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(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毫克褪黑素可以将9名年轻盲人中的8名自由奔跑的昼夜节律引入(同步)到24小时的一天，从而改善夜间睡眠和白天的警觉性。未携带的患者治疗前自由奔跑时间最长(24.9h)。此外，我们已经证明，当盲人受试者自由奔跑的昼夜节律颠倒时，10毫克的褪黑素具有直接的催眠作用。最近，我们发现，在这些人中，有三分之一的人可以将剂量降低到0.5毫克。我们进一步发现，它们也可以被携带到从头开始的0.5 mg剂量(它们的最长自由运行时间为24.4h)。预处理期似乎可以预测褪黑素的包埋可能性和包埋的稳定阶段，这与动物研究中建立的几个重要原则是一致的。因此，我们的项目具有临床和科学两方面的重要性。美国大约有20万完全失明的人。其中约50%的人有自由奔跑的昼夜节律。这些人中有许多是老年人。该项目的目标将是确定三种剂量(0.5毫克、10毫克和20毫克)的褪黑素治疗效果，并预测0.5毫克的剂量只对病程相对较短(24.5小时)的人有效。对于0.5毫克剂量的治疗失败，我们将测试更高剂量的疗效。成功携带褪黑激素的盲人受试者将接受为期一年的跟踪，以评估服用褪黑激素的长期益处和风险。研究老年盲人尤为重要，因为与年轻盲人相比，他们可能更容易受到褪黑素的副作用的影响，而且他们对褪黑素治疗的反应可能会有所不同。在我们将要解决的许多基础科学问题中，年龄对昼夜节律的影响。对盲人的研究提供了一个机会，让我们了解不受光/暗周期干扰的人类昼夜节律系统的生理学。