Official Title: “Melatonin Entrainment of Elderly Blind Free-Runners”

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.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Single Blind (Subject), Uncontrolled, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: May 2008

We 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).

Intervention(s) in this Clinical Trial

• Dietary Supplement: Melatonin
  • 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.
• Dietary Supplement: Melatonin
  • 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.
• Dietary Supplement: Melatonin
  • 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.
• Dietary Supplement: Melatonin
  • 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Subjects will be given 0.5 mg at a time when melatonin should delay the timing of their body clock. If the subject's body clock responds successfully to the dose, the dose will be reduced gradually until the lowest effective dose is found. If the treatment does not work, the subject will be taken off treatment and later entered into a new treatment regimen.
• Experimental: 2
  • Subjects will be given 0.5 mg at a time when melatonin should advance the timing of their body clock. If the subject's body clock responds successfully to the dose, the dose will be reduced gradually until the lowest effective dose is found. If the treatment does not work, the subject will be taken off treatment and later entered into a new treatment regimen.
• Experimental: 3
  • Subjects will be given a larger dose (up to 10 mg) at a time when the melatonin should advance the timing of the body clock. If the subject's body clock responds successfully to the dose, the dose will be reduced gradually until the lowest effective dose is found. If the treatment does not work, the subject will be taken off treatment and later entered into a new treatment regimen.
• Experimental: 4
  • Subjects will be given a larger dose (up to 20 mg) at a time when the melatonin should advance the timing of the body clock. If the subject successfully responds to the treatment, the dose will be reduced gradually until the lowest effective dose is determined (down to 0.025 mg). If the treatment does not work, the subject will be taken off treatment and later entered into a new treatment regimen.

Primary Measures

• Circadian phase marker, as measured by the melatonin levels in serial salivary and/or plasma samples.
  • Time Frame: biweekly throughout the entire study
    Safety Issue?: No

Secondary Measures

• Durability and Toxicity Side Effects Questionnaire
  • Time Frame: 1 year
    Safety Issue?: Yes

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;
• and 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);
• or external demands that limit the ability to maintain a regular schedule, e.g. night shift work.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 55 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Oregon Health and Science University

Overall Clinical Trial Officials and Contacts

Alfred J Lewy, MD, PhD Principal Investigator Oregon Health and Science University  

Overall Contact: Jeannie B Songer, B.A. 503-418-4144 songerj@ohsu.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00692094

Study ID Number: eIRB 0194

ClinicalTrials.gov Identifier: NCT00692094

Health Authority: United States: Food and Drug Administration

OHSU Sleep and Mood Disorders Laboratory website