Blind Elderly Melatonin Treatment Study

Study Overview
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Brief Summary
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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
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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).

Official Title
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Melatonin Entrainment of Elderly Blind Free-runners

Conditions
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Blindness

Intervention / Treatment
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* Biological: Melatonin
* Biological: Melatonin
* Biological: Melatonin
* Biological: Melatonin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.<br>|
| Experimental: 2<br>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<br>* 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.<br>|
| Experimental: 3<br>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<br>* 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.<br>|
| Experimental: 4<br>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<br>* 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melatonin, circadian rhythms, sleep