This protocol describes a multicenter clinical trial of melatonin for sleep disturbances associated with Alzheimer's Disease (AD). Frequent nocturnal awakening is a common behavioral symptom of AD. Nighttime wandering and agitated behavior may result in injuries and sleep disruption for caregivers. Alternatives are sorely needed to the currently available sleep medications which have marginal efficacy and serious side effects. Melatonin is a naturally occurring hormone secreted by the pineal gland. It has soporific effects with oral administration and is well tolerated. It is reasonable to suspect that melatonin may help sleep disturbances associated with AD, however, this remains to be proven. The proposed study is a randomized, double blind, parallel group, placebo controlled, clinical trial. Placebo will be compared with two doses of melatonin: a 0.5 mg, slow release preparation and a 10 mg immediate release preparation. One hundred forty-seven community-residing AD patients with disrupted sleep will be recruited. Included subjects will meet NINCDS-ADRDA criteria for probable AD. Prior to study entry, disrupted sleep will be documented by clinical history and by two weeks of recordings using wrist activity monitors. The treatment period will last eight weeks. Rest/activity patterns will be recorded by wrist activity monitors. The primary outcome measure will be the change in nocturnal sleep time from baseline to the end of the treatment phase. Other outcomes will also be examined, including the time awake after sleep onset, sleep latency, sleep efficiency and daytime agitation. The relative effectiveness of high and low dose melatonin will be assessed. Adverse events and side effects will be compared by treatment This study should provide the data necessary to determine whether melatonin is a safe and effective treatment for disrupted sleep associated with AD.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project--Cooperative Agreements (U01)
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University of California San Diego
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