Blind Elderly Melatonin Treatment Study

NCT ID: NCT00692094

Last Updated: 2019-11-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2008-12-31

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).

Conditions

Blindness

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: BIOLOGICAL

0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.

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.

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: BIOLOGICAL

0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.

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.

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: BIOLOGICAL

0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.

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.

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: BIOLOGICAL

0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.

Interventions

Melatonin

0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.

Intervention Type: BIOLOGICAL

Melatonin

0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.

Intervention Type: BIOLOGICAL

Melatonin

0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.

Intervention Type: BIOLOGICAL

Melatonin

0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfred J Lewy, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

Locations

Sleep and Mood Disorders Lab, Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 10810544 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11027741 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11684046 (View on PubMed)

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.

Reference Type: RESULT

PMID: 16393710 (View on PubMed)

Other Identifiers

R01AG021826

Identifier Type: NIH

Identifier Source: secondary_id

View Link

eIRB 0194

Identifier Type: -

Identifier Source: org_study_id