Clinical trial NCT00692094: Blind Elderly Melatonin Treatment Study
Official title: Melatonin Entrainment of Elderly Blind Free-runners
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Blindness
Keywords: melatonin
circadian rhythms
sleep
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2008-06-06
Enrollment: 12
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary focus of this five-year study will be to optimize the melatonin dosing regimen for synchronizing the body clocks of elderly blind individuals to the 24-hour day.

Detailed description: The investigators intend to study as many as 26 subjects through up to four melatonin treatment regimens, all of which involve a dose step-down in which the melatonin dose will be reduced gradually to find the lowest effective dose. The 4 treatment plans differ only in the start dose and the time of administration. Successfully treated subjects will enter a one-year intensive assessment of the safety and efficacy of melatonin treatment in which the subject will take the same dose for one year and complete biweekly assessments of efficacy and side-effects. The final phase of the study involves a placebo discontinuation, in which the subject's circadian rhythm will be returned to the baseline rhythm (this may take up to 6 months for some subjects).

Eligibility criteria: Inclusion Criteria:

* Adults 55-100 years old
* Blindness for at least one year, verified by an ophthalmologic exam
* Ability to comply with the requirements of the experimental protocol
* No clinically significant abnormalities (other than blindness) on a general physical examination
* Subjects must be competent to sign informed consent

Exclusion Criteria:

* Abnormal heart, liver or kidney function; a current Axis I psychiatric or substance abuse disorder according to the DSM-IV Manual
* A diagnosis of obstructive sleep apnea (apnea index \> 10) or nocturnal myoclonus (\> 10 associated arousals/hour)
* External demands that limit the ability to maintain a regular schedule, e.g., night shift work

Primary outcomes:
measure: Circadian Phase Marker, as Measured by the Melatonin Levels in Serial Salivary and/or Plasma Samples.
timeFrame: biweekly throughout the entire study
Secondary outcomes:
measure: Durability and Toxicity Side Effects Questionnaire
timeFrame: 1 year
Other outcomes:
Locations:
city: Portland
country: United States
facility: Sleep and Mood Disorders Lab, Oregon Health & Science University
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Alfred J Lewy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lewy AJ. Melatonin as a marker and phase-resetter of circadian rhythms in humans. Adv Exp Med Biol. 1999;460:425-34. doi: 10.1007/0-306-46814-x_51. No abstract available.
citation: Sack RL, Brandes RW, Kendall AR, Lewy AJ. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med. 2000 Oct 12;343(15):1070-7. doi: 10.1056/NEJM200010123431503.
citation: Lewy AJ, Bauer VK, Hasler BP, Kendall AR, Pires ML, Sack RL. Capturing the circadian rhythms of free-running blind people with 0.5 mg melatonin. Brain Res. 2001 Nov 9;918(1-2):96-100. doi: 10.1016/s0006-8993(01)02964-x.
citation: Lewy AJ, Emens JS, Lefler BJ, Yuhas K, Jackman AR. Melatonin entrains free-running blind people according to a physiological dose-response curve. Chronobiol Int. 2005;22(6):1093-106. doi: 10.1080/07420520500398064.