Blind Child Melatonin Treatment Study

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00691444
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 10
• Location: 1
• Arms: 3
• Duration (Months): 159
• Patients Per Site Per Month: 0.1

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 blind children to the 24-hour day.

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

Detailed Description

We intend to study as many as 26 blind children through up to three 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 3 treatment plans differ only in the start dose. Successfully treated subjects (of one treatment plan) 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: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: Melatonin Studies of Blind Children
• Study Start Date: Sep 1, 2002
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Subjects will be given up to 0.5 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan.	Dietary Supplement: Melatonin; Subjects will be given up to 0.5 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).
Experimental: 2 Subjects will be given up to 10 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan.	Dietary Supplement: Melatonin; Subjects will be given up to 10 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).
Experimental: 3 Subjects will be given up to 20 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan.	Biological: Melatonin; Subjects will be given up to 20 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).

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: 5 Years to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Children and adults 5 to 20 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 if age 18 or older. Parents and subjects will be interviewed together and, when appropriate (for example, subject is age 18 or older), separately as well.

Exclusion Criteria:

• Abnormal heart, liver or kidney function; intractable seizure disorders

• Significant laboratory abnormalities on CBC, Comprehensive Metabolic set, or UA (dip stick method)

• Pregnancy; sexual activity in post-pubertal females not using a recognized and valid contraceptive method

• A current Axis I psychiatric or substance abuse disorder according to the DSM-IV Manual ; OR

• 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
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• Lewy AJ, Emens J, Jackman A, Yuhas K. Circadian uses of melatonin in humans. Chronobiol Int. 2006;23(1-2):403-12. Review.
• Stores G, Ramchandani P. Sleep disorders in visually impaired children. Dev Med Child Neurol. 1999 May;41(5):348-52. Review.

• Responsible Party: Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT00691444
• Other Study ID Numbers: eIRB 1251; R01HD042125
• First Posted: Jun 5, 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	0.5mg Melatonin	10mg Melatonin	20mg Melatonin
Arm/Group Description	Subjects will be given up to 0.5 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 0.5 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 10 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 10 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 20 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 20 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).
Period Title: Overall Study
STARTED	0	0	0
COMPLETED	0	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	0.5mg Melatonin	10mg Melatonin	20mg Melatonin	Total
Arm/Group Description	Subjects will be given up to 0.5 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 0.5 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 10 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 10 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 20 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 20 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Total of all reporting groups
Overall Participants	0	0	0	0
Age () []
Sex: Female, Male () []
Female
Male
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	0.5mg Melatonin	10mg Melatonin	20mg Melatonin
Arm/Group Description	Subjects will be given up to 0.5 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 0.5 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 10 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 10 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 20 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 20 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).
Measure Participants	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	0.5mg Melatonin	10mg Melatonin	20mg Melatonin
Arm/Group Description	Subjects will be given up to 0.5 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 0.5 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 10 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 10 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).	Subjects will be given up to 20 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 20 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).
Measure Participants	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	0.5mg Melatonin		10mg Melatonin		20mg Melatonin
Arm/Group Description	Subjects will be given up to 0.5 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 0.5 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).		Subjects will be given up to 10 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 10 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).		Subjects will be given up to 20 mg daily. If the treatment works, the dose will be reduced gradually until the lowest, effective dose is identified. If the treatment is unsuccessful, the subject will be taken off treatment and later enrolled in a different treatment plan. Melatonin: Subjects will be given up to 20 mg daily. 0.005-20 mg, daily, up to 5 years (the exact duration depends on each subjects response to the dose and the specifics of their circadian rhythm patterns).
All Cause Mortality
	0.5mg Melatonin		10mg Melatonin		20mg Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	0.5mg Melatonin		10mg Melatonin		20mg Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	0.5mg Melatonin		10mg Melatonin		20mg Melatonin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	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.