Sleep Disorders, Circadian Rhythm Clinical Trial
Official title:
A Phase One Treatment Trial of the Circadian Sleep Disturbance in Smith-Magenis Syndrome (SMS)
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.
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 melatonin
levels in children with Smith-Magenis syndrome (SMS). We predict that the inverse pattern of
release can be corrected by the combination of non-pharmacological suppression of daytime
melatonin release and pharmacological replacement of nocturnal melatonin. Negative behaviors
associated with accumulated sleep debt are expected to diminish as sleep quality improves.
Two treatment modalities will be evaluated alone and in combination: 1) light-induced
suppression of daytime melatonin release and delay of nighttime sleep; and 2) pharmacological
replacement of nocturnal melatonin. Melatonin levels measured in blood (Pre- vs.
Post-treatment) will serve as the primary outcome parameter. A dTR-melatonin tablet developed
by the Clinical Center Pharmaceutical Development Services (CC-PDS) will be used in this
trial.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05346588 -
THRIVE Feasibility Trial
|
Phase 3 | |
Recruiting |
NCT05991453 -
Trajectories of Recovery After Intravenous Propofol Versus Inhaled VolatilE Anesthesia Trial
|
N/A | |
Withdrawn |
NCT05096130 -
Lifestyle Medicine Strategies for Combating Sleepiness and Fatigue in Professional Drivers
|
N/A | |
Completed |
NCT01327040 -
Light Sensitization Study
|
N/A | |
Completed |
NCT00593736 -
Efficacy of Ramelteon on Speeding Up Sleep in Subjects With Delayed Sleep Phase Syndrome
|
Phase 2 | |
Recruiting |
NCT00387179 -
Effectiveness of Combining Light and Non-Light Treatments for Jet Lag and Sleep Disorders
|
N/A | |
Recruiting |
NCT04900675 -
Bright Light Intervention to Reduce Students' Stress
|
N/A | |
Completed |
NCT01881854 -
Sleep Wake and Melatonin Pattern in Craniopharyngioma
|
N/A | |
Completed |
NCT00246051 -
Comprehensive Police Fatigue Management Program
|
N/A | |
Recruiting |
NCT04690504 -
Validation of Circadian Biomarkers in Patients With Sleep Disorders
|
||
Completed |
NCT03363529 -
ROOM-LIGHT: Dynamic LED-light as Treatment for Depressed Patients in Inpatient Wards
|
N/A | |
Recruiting |
NCT05701969 -
Effect of Melatonin on Sleep Patterns of Resident Trainees During Night Float Shift
|
Early Phase 1 | |
Completed |
NCT00723580 -
Actigraphic Analysis of Treatment Response
|
N/A | |
Completed |
NCT00207285 -
Sleep Disorders Management, Health and Safety in Police
|
N/A | |
Not yet recruiting |
NCT06336525 -
Adult Sleep Health in the Rural Appalachia and Mississippi Delta Region and Its Relationships With Cardiometabolic Health Disparities.
|
||
Recruiting |
NCT05618405 -
Changes in Circadian Rhythm After Anaesthesia in Children
|
||
Completed |
NCT05684523 -
Feasibility Study on the Use of Redormin®500 on Day-time Cognition
|
Phase 4 | |
Recruiting |
NCT05247125 -
The Role of Circadian Factors in Regulation of Neuroplasticity in Ischemic Stroke (Interventional)
|
Phase 4 | |
Completed |
NCT04219566 -
Vestibular Nerve Stimulation to Improve Sleep
|
N/A | |
Not yet recruiting |
NCT06233422 -
Longitudinal Ecological Study on Sleep-Wake Patterns in MDD Using Actigraphy
|