Treatment Strategies for Children With Smith-Magenis Syndrome

Summary

This study will examine the effect of bright light or melatonin treatment on sleep in children with Smith-Magenis syndrome (SMS), a genetic disorder characterized by certain physical, behavioral and developmental features. Patients have a disrupted sleep cycle involving early waking, frequent daytime napping and frequent nighttime awakenings. Melatonin is a hormone normally produced at night in healthy people. People with SMS produce high levels of melatonin during the daytime and very low levels at night. This may affect their behavior, mood, attention span and sleep patterns.

Healthy volunteers between 18 and 45 years of age and children with SMS who are between 3 and 16 years of age may be eligible for this study.

Healthy subjects are admitted to the NIH Clinical Center overnight. In the morning they take one dose of time-release melatonin and have blood and saliva samples collected hourly from 7:00 AM to 6:00 PM.

Children with SMS participate in a 2-part study, as follows:

Part 1 Inpatient Trial

Pre-trial at-home phase: During the month before NIH inpatient admission, participants do the following:

* Wear an actiwatch device or keep a daily sleep diary to monitor daytime alertness, mood shifts and sleep patterns.
* Complete a behavior assessment survey related to the child s behaviors and sleep patterns.
* Obtain frequent body temperature measurements.
* Collect several saliva samples over a 24-hour period.

NIH admission phase:

* Children are admitted to the NIH Clinical Center for 2-3 nights for bright light treatment. They remain in their rooms for alternating periods of exposure to standard dim room light and bright light, using a light box placed within 3 to 5 feet of the child. An electroencephalogram (EEG) with additional electrodes to track eye movements is used to monitor the child s attention. Between 8AM and 6PM serial blood samples are collected to measure melatonin levels. A parent rates the child s mood and behavior during the 2-day test period.
* Children are admitted to the NIH Clinical Center for 2-3 nights for melatonin treatment. They take a single dose of melatonin or placebo tablet at bedtime. During the daytime, EEG electrodes are placed to track eye movements. Between 7 PM and 7 AM serial blood samples are collected to measure melatonin levels. A parent rates the child s behavior and mood as described for the bright light study.
* Children may receive either or both of the bright light and melatonin treatments.

Part 2 Outpatient Trial

Children participate in a combined bright light with melatonin trial at home. They undergo the same procedures outlined in the pre-trial at-home phase of Part 1 (actiwatch, behavior assessments, body temperature measurements, saliva samples) over an 11-week period. If saliva samples cannot be collected for melatonin testing, 24-hour urine samples may be collected instead.

Conditions

• Developmental Delay Disorders
• Chromosome Deletion
• Mental Retardation
• Sleep Disorders, Circadian Rhythm
• Self Injurious Behavior

Interventions

DRUG

dTR Melatonin (NIH CC PDS)

DEVICE

Phototherapy (Bright Light)

DRUG

Melatonin CR

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI)

  lead NIH

Principal Investigators

• William A Gahl, M.D. · National Human Genome Research Institute (NHGRI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Model

CROSSOVER

Eligibility

Min Age

3 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-07-17

Primary Completion

2018-05-22

Completion

2018-05-22

Countries

• United States

Study Locations