Melatonin Entrainment of Elderly Blind Free-runners

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 (