Study of Melatonin: Sleep Problems in Alzheimer's Disease

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This protocol is 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 that 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 enhances sleep in normal older people. Melatonin also may help sleep disturbances associated with AD; however, this remains to be proven.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute on Aging (NIA)
• Treatments: Melatonin

Criteria

Inclusion Criteria:

• Patients must meet NINCDS-ADRDA criteria for probable Alzheimer's disease (AD). Patients must have disrupted sleep, documented by clinical history and by 1 to 2 weeks of recording using wrist activity monitors.

• A diagnosis of probable AD.

• MMSE score 0-26.

• Hachinski Ischemia Scale score less than or equal to 4.

• A 2-week history of two or more sleep disorder behaviors, occurring at least once weekly, as reported by the caregiver on the Sleep Disorder Inventory.

• CT or MRI since the onset of memory problems showing no more than one lacunar infarct in a non-strategic area and no clinical events suggestive of stroke or other intracranial disease since the CT or MRI.

• Physically acceptable for study as confirmed by medical history and exam, clinical laboratory results, and EKG.

• Actigraph evidence of a mean nocturnal sleep time of less than 7 hours per night (at least 5 nights of complete actigraph data must be collected over a single week.

• Stable home situation with no planned move during the 13-week investigational period.

• Residing with responsible spouse, family member, or professional caregiver who is present during the night and will agree to assume the role of the principal caregiver for the 13-week protocol, including arranging transport for the patient to and from the investigators' clinic, answering questions regarding the patient's condition, and assuming responsibility for medication and actigraph procedures.

• Ability to ingest oral medication and participate in all scheduled evaluations.

• Six grades of education or work history sufficient to exclude mental retardation.

• 55 years of age or older.

• Hamilton Depression Rating Scale score of 15 or less.

• Stable medication (dose and type) for non-excluded concurrent medical conditions for 4 weeks prior to the screening visit.

Exclusion Criteria:

• Sleep disturbance is acute (within the last 2 weeks).

• Sleep disturbance is associated with an acute illness with delirium.

• Clinically significant movement disorder that would interfere with the actigraph readings.

• Not having a mobile upper extremity to which to attach an actigraph.

• Severe agitation.

• Pain syndrome affecting sleep.

• Unstable medical condition.

• Use of investigational or unapproved medications within 4 weeks of the screening visit.

• Patient unwilling to maintain caffeine abstinence after 2:00 pm for the duration of the protocol.

• Patient unwilling to comply with the maximum limit of two alcoholic drinks per day, and only one alcoholic drink after 6:00 pm for the duration of the protocol.

• Use of melatonin within 2 weeks of screening visit.

• Clinically significant abnormal laboratory findings that have not been approved by the Project Director.

• Residing in a facility without a consistent caregiver present during the night who can function as the primary informant.

• Caregiver deemed too unreliable to supervise the wearing of the actigraph, to maintain the sleep diary, or to bring the patient to the scheduled visits.

• Autoimmune disease, such as rheumatoid arthritis and polymyalgia rheumatica.