Blind Elderly Melatonin Treatment Study

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00692094
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 12
• Location: 1
• Arms: 4
• Duration (Months): 52
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Blindness	Biological: Melatonin; Biological: Melatonin; Biological: Melatonin; Biological: Melatonin	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Melatonin Entrainment of Elderly Blind Free-runners
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

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.
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, at a time when melatonin should advance the timing of their 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 - 10 mg, daily, at a time when melatonin should advance the timing of their 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 - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.

Outcome Measures

Primary Outcome Measures

1. Circadian Phase Marker, as Measured by the Melatonin Levels in Serial Salivary and/or Plasma Samples. [biweekly throughout the entire study]

Secondary Outcome Measures

1. Durability and Toxicity Side Effects Questionnaire [1 year]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sleep and Mood Disorders Lab, Oregon Health & Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

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.
• Lewy AJ. Melatonin as a marker and phase-resetter of circadian rhythms in humans. Adv Exp Med Biol. 1999;460:425-34. Review.
• 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.

• Responsible Party: Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT00692094
• Other Study ID Numbers: eIRB 0194; R01AG021826
• First Posted: Jun 6, 2008
• Last Update Posted: Nov 27, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by Oregon Health and Science University: melatonin; circadian rhythms; sleep
• Additional relevant MeSH terms: Blindness; Melatonin

Study Results

Participant Flow

Pre-assignment Detail	The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.

Arm/Group Title	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)	Melatonin: 0.025 mg - 0.5 mg (Advance Timing)	Melatonin: 0.025 mg - 10 mg (Advance Timing)	Melatonin: 0.025 mg - 20 mg (Advance Timing)
Arm/Group Description	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. Melatonin: 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.	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. Melatonin: 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
Period Title: Overall Study
STARTED	0	0	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)	Melatonin: 0.025 mg - 0.5 mg (Advance Timing)	Melatonin: 0.025 mg - 10 mg (Advance Timing)	Melatonin: 0.025 mg - 20 mg (Advance Timing)	Total
Arm/Group Description	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. Melatonin: 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.	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. Melatonin: 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.	Total of all reporting groups
Overall Participants	0	0	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Race and Ethnicity Not Collected () []
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.

Arm/Group Title	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)	Melatonin: 0.025 mg - 0.5 mg (Advance Timing)	Melatonin: 0.025 mg - 10 mg (Advance Timing)	Melatonin: 0.025 mg - 20 mg (Advance Timing)
Arm/Group Description	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. Melatonin: 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.	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. Melatonin: 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
Measure Participants	0	0	0	0

2. Secondary Outcome

Title	Durability and Toxicity Side Effects Questionnaire
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.

Arm/Group Title	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)	Melatonin: 0.025 mg - 0.5 mg (Advance Timing)	Melatonin: 0.025 mg - 10 mg (Advance Timing)	Melatonin: 0.025 mg - 20 mg (Advance Timing)
Arm/Group Description	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. Melatonin: 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.	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. Melatonin: 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.	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. Melatonin: 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
Measure Participants	0	0	0	0

Adverse Events

Adverse Event Reporting Description	The PI has retired from the institution. Sincere efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Arm/Group Title	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)		Melatonin: 0.025 mg - 0.5 mg (Advance Timing)		Melatonin: 0.025 mg - 10 mg (Advance Timing)		Melatonin: 0.025 mg - 20 mg (Advance Timing)
Arm/Group Description	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. Melatonin: 0.025 mg-0.5 mg, daily given at a time when it is expected to delay the timing of the body clock.		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. Melatonin: 0.025 mg - 0.5 mg, daily, at a time when melatonin should advance the timing of their body clock.		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. Melatonin: 0.025 mg - 10 mg, daily, at a time when melatonin should advance the timing of their body clock.		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. Melatonin: 0.025 mg - 20 mg, daily, at a time when the melatonin should advance the timing of the body clock.
All Cause Mortality
	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)		Melatonin: 0.025 mg - 0.5 mg (Advance Timing)		Melatonin: 0.025 mg - 10 mg (Advance Timing)		Melatonin: 0.025 mg - 20 mg (Advance Timing)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)		Melatonin: 0.025 mg - 0.5 mg (Advance Timing)		Melatonin: 0.025 mg - 10 mg (Advance Timing)		Melatonin: 0.025 mg - 20 mg (Advance Timing)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Melatonin: 0.025 Mg-0.5 mg (Delay Timing)		Melatonin: 0.025 mg - 0.5 mg (Advance Timing)		Melatonin: 0.025 mg - 10 mg (Advance Timing)		Melatonin: 0.025 mg - 20 mg (Advance Timing)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Analyses were not completed because, a unique provision in the American Recovery and Reinvestment Act (ARRA) of 2009 funding source unexpectedly prevented approval of a second year no-cost-extension in which completion of analyses were planned.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.