Clinical Trial: Treatment Strategies for Children With Smith-Magenis Syndrome

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase One Treatment Trial of the Circadian Sleep Disturbance in Smith-Magenis Syndrome (SMS)

Brief 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:

    Detailed Summary:

    Smith-Magenis syndrome (SMS) is a rare (1/25,000) clinically recognizable syndrome, characterized by the following features: a distinct pattern of minor craniofacial and skeletal anomalies, expressive speech/language delays, psychomotor and growth retardation, and a striking neurobehavioral phenotype. This phenotype includes stereotypies, self-injurious and aggressive behaviors, and a chronic sleep disorder associated with an inverted circadian melatonin rhythm. Sleep disturbances include daytime sleepiness, early sleep onset, and early morning awakening. Disturbed sleep is the strongest predictor of maladaptive behavior in children with SMS. Diminished nocturnal sleep is virtually universal in SMS, representing a major challenge to the patient and family. The majority (greater than 95%) of cases are due to interstitial deletion of 17p11.2; however, rare cases due to RAI1 gene mutations are also reported.

    One of the likely contributing factors to these sleep disturbances is an inverse circadian pattern of the sleep-promoting hormone, melatonin. In SMS, plasma melatonin is high during the day and low at night, which is opposite the normal pattern. The underlying reason for this regular daytime melatonin secretory pattern is unknown. To our knowledge this pattern is distinctive to persons with SMS and not found elsewhere. SMS therefore offers a unique human syndrome for the study of melatonin function. At the present time, there is no effective treatment for sleep disturbances in SMS. Moreover, there are currently no controlled treatment trials underway in the U.S. with the specific goal of correcting the disturbed sleep pattern observed in this disease.

    The aim of this Phase 1 treatment trial is to improve the quality of nocturnal sleep and decrease the need for daytime sleep by restoring a normal circadian pattern of melat
    Sponsor: National Human Genome Research Institute (NHGRI)

    Current Primary Outcome: Change in level of melatonin (pg/ml) from baseline

    Original Primary Outcome: Same as current

    Current Secondary Outcome: Improved sleep parameters (actigraphy). Increased daytime vigilance. Decreased maladaptive behaviors.

    Original Secondary Outcome: -Improved sleep parameters (actigraphy)@@@-Increased daytime vigilance@@@-Decreased maladaptive behaviors

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: July 21, 2007
    Date Started: July 17, 2007
    Date Completion: June 1, 2017
    Last Updated: April 20, 2017
    Last Verified: February 10, 2017