Chronic insomnia affects up to 35% of the elderly. It can significantly impair quality of life and daytime functioning. Currently, most medical therapy for insomnia involves sedative-hypnotic agents that may lead to dependence, withdrawal side effects and reduced efficacy after extended periods of use. A growing body of work has suggested that melatonin, a neurohormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, the primary circadian pacemaker, may play a role in mediating insomnia. Ongoing research at the University of Pennsylvania in 180 elderly insomnia patients has found statistically significant evidence of a decreased sleep efficiency in low melatonin insomniacs. Thus, melatonin production is impaired in a subgroup of elderly insomnia patients and this may contribute to their insomnia. However, melatonin treatment trials in elderly insomniacs have been equivocal. These studies have had serious methodologic limitations including inadequate sample size (Type II error), lack of objective measures of sleep or daytime functioning, and no placebo control arm. This has raised many questions such as whether melatonin deficiency is a marker of insomnia or, instead, a contributing factor and whether increased doses are needed to recreate the higher levels seen in the cerebrospinal fluid compartment. In addition, melatonin is widely used as an over-the-counter sleeping aid with litre true insight into its effectiveness/safety, especially in older adults. To address the primary hypothesis that melatonin can treat insomnia in melatonin-deficient elderly, the principal investigator proposes conducting a large randomized, double-blind clinical trial comparing low dose melatonin (0.4 mg), high dose melatonin (4.0 mg) and placebo in a well-defined group of elderly insomniacs with low melatonin levels (189 total subjects).
The specific aims are to 1) evaluate the effectiveness of melatonin and 2) assess the daytime consequences and safety of melatonin treatment in this population. Intention-to-treat analysis will compare low dose melatonin, high dose melatonin, and placebo on objective and subjective parameters of sleep and daytime function. This protocol will extend well beyond the research done to date by rigorously testing the role of targeted melatonin replacement therapy as an effective treatment for insomnia in the elderly and by evaluating the safety profile of melatonin with a particular focus on daytime functioning.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
1R01AT001521-01A1
Application #
6722637
Study Section
Brain Disorders and Clinical Neuroscience 5 (BDCN)
Program Officer
Pearson, Nancy
Project Start
2003-09-22
Project End
2007-05-31
Budget Start
2003-09-22
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$345,100
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Gooneratne, Nalaka S; Vitiello, Michael V (2014) Sleep in older adults: normative changes, sleep disorders, and treatment options. Clin Geriatr Med 30:591-627
Gooneratne, Nalaka S; Edwards, Alena Y Z; Zhou, Chen et al. (2012) Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults. J Pineal Res 52:437-45
Gooneratne, Nalaka S; Bellamy, Scarlett L; Pack, Frances et al. (2011) Case-control study of subjective and objective differences in sleep patterns in older adults with insomnia symptoms. J Sleep Res 20:434-44
Gooneratne, Nalaka S (2008) Complementary and alternative medicine for sleep disturbances in older adults. Clin Geriatr Med 24:121-38, viii
Gooneratne, Nalaka S; Gehrman, Philip R; Nkwuo, J Emeka et al. (2006) Consequences of comorbid insomnia symptoms and sleep-related breathing disorder in elderly subjects. Arch Intern Med 166:1732-8