Blind Elderly Melatonin Treatment Study

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 Overview

• Status: Terminated
• Conditions: Blindness
• Intervention / Treatment: Biological: Melatonin; Biological: Melatonin; Biological: Melatonin; Biological: Melatonin

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).

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Sleep and Mood Disorders Lab, Oregon Health & Science University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Biological: Melatonin; 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.; Biological: Melatonin; 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
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.	Biological: Melatonin; 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.; Biological: Melatonin; 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
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.	Biological: Melatonin; 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.; Biological: Melatonin; 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
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.	Biological: Melatonin; 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.; Biological: Melatonin; 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.; Biological: Melatonin; 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Circadian Phase Marker, as Measured by the Melatonin Levels in Serial Salivary and/or Plasma Samples.	biweekly throughout the entire study

Secondary Outcome Measures

Outcome Measure	Time Frame
Durability and Toxicity Side Effects Questionnaire	1 year

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: May 30, 2008
• First Submitted That Met QC Criteria: June 4, 2008
• First Posted (Estimate): June 6, 2008

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: sleep; melatonin; circadian rhythms
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Sensation Disorders; Vision Disorders; Blindness; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: eIRB 0194; R01AG021826 (U.S. NIH Grant/Contract)