Study of Melatonin: Sleep Problems in Alzheimer's Disease

Sponsor

National Institute on Aging (NIA) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000171

Collaborator

(none)

Locations

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease Dyssomnias	Drug: Melatonin	Phase 3

Detailed Description

In Alzheimer's disease , sleep disruption is one of the most common behavioral problems, occurring in 45 percent of patients. These nocturnal awakenings and agitation lead to considerable burden for caregivers and frequently lead families to the decision of nursing home placement. The proposed study is a randomized, double blind, parallel group, placebo controlled, clinical trial. Placebo will be compared with two doses of melatonin: a 2.5 mg, slow- release preparation and a 10 mg immediate release preparation. One hundred and fifty 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 1 to 2 weeks of recording using wrist activity monitors. The treatment period will last 8 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 also will be examined, including the time awake after sleep onset, sleep latency, sleep efficiency, daytime agitation, and changes in cognition. 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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85724-5023
2	University of California Irvine Institute for Brain Aging and Dementia	Irvine	California	United States	92697-4285
3	University of California, San Diego	La Jolla	California	United States	92037
4	University of Southern California	Los Angeles	California	United States	90033-1039
5	University of California, Los Angeles	Los Angeles	California	United States	90095-1769
6	Yale University, Alzheimer's Disease ResearchUnit	New Haven	Connecticut	United States	06520-8037
7	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32225
8	Mount Sinai (Miami)	Miami	Florida	United States	33140
9	University of South Florida	Tampa	Florida	United States
10	Emory University	Atlanta	Georgia	United States	30329
11	Augusta VA Medical Center	Augusta	Georgia	United States	30904
12	Southern Illinois University	Springfield	Illinois	United States	62702
13	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
14	University of Kentucky	Lexington	Kentucky	United States	40536-0230
15	Johns Hopkins University	Baltimore	Maryland	United States	21224
16	University of Michigan	Ann Arbor	Michigan	United States	48109
17	University of Minnesota	Minneapolis	Minnesota	United States	55455
18	Mayo Clinic at Rochester	Rochester	Minnesota	United States	14620
19	Washington University	St. Louis	Missouri	United States	63110
20	New York University Medical Center	New York	New York	United States	10016
21	Columbia University	New York	New York	United States	11032
22	University of Rochester Medical Center	Rochester	New York	United States	14620
23	University Hospitals of Cleveland	Cleveland	Ohio	United States	44120
24	Oregon Health Sciences University	Portland	Oregon	United States	97201-3098
25	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104-4283
26	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
27	Brown University	Pawtucket	Rhode Island	United States	02860
28	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212-8646
29	University of Texas	Dallas	Texas	United States	75235
30	Baylor College of Medicine	Houston	Texas	United States	77030
31	University of Washington	Seattle	Washington	United States	98108