Treatment Strategies for Children With Smith-Magenis Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00506259
• Date of registration: 21/07/2007
• Prospective Registration: No
• Primary sponsor: National Human Genome Research Institute (NHGRI)
• Public title: Treatment Strategies for Children With Smith-Magenis Syndrome
• Scientific title: A Phase One Treatment Trial of the Circadian Sleep Disturbance in Smith-Magenis Syndrome (SMS)
• Date of first enrolment: July 17, 2007
• Target sample size: 23
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00506259
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment.
• Phase: Phase 1

Countries of recruitment

United States

Contacts

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

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

SMS subjects enrolled in protocol 01-HG-0109 will be invited to participate in this study.
Protocol 01-HG-0109 has approximately 90 SMS subjects.

SMS inpatient admissions for the dTR-MT trial will be deferred until the BL study completes
10 SMS subjects who demonstrate expected SMS inverted diurnal MT profiles at baseline (T0).

SMS Subjects (N=12-15 per each treatment goal; 60 total enrollment):

- Male and female, childhood (average 5-16 years old; under age 5 years on case-by-case
basis), all ethnicities with confirmed diagnosis of SMS (del 17p11.2). In some cases,
molecular cytogenetic FISH screening (RAI1 FISH probe) may be required to confirm the
SMS diagnosis prior to enrollment.

- Prepubertal (less than or equal to Tanner stage II).

- No history of seizures

- Priority will be given to subjects who are medication free and/or willing to
discontinue sleep/behavioral medications during the study trial. We anticipate
significant interest from families whose children are currently enrolled in the
01-HG-0109 protocol. We will also consider drug-free new referrals (self-referrals
and/or via health care providers) eligible for enrollment.

- Documented sleep disturbance (by sleep log diary and/or actigraphy).

Unaffected Healthy Control Subjects (N=15). The pharmacokinetics of melatonin release by
the dTR tablet will be evaluated in unaffected healthy control subjects prior to use in the
inpatient SMS trial.

- Males and females of any ethnicity and between the ages 18-45 years.

- Regular (11PM - 7AM) sleep schedule for at least 1 week prior to study.

- Non-smokers, who have no history of seizures.

- Willing to discontinue coffee consumption for a period of 1-2 weeks prior to trial.

- BMI within normal limits (10-90 percentile).

- Unaffected with SMS.

EXCLUSION CRITERIA:

SMS Subjects:

- Inability to obtain informed consent.

- Failure to confirm clinical diagnosis of SMS by standard molecular cytogenetic (FISH)
methods and/or DNA-based mutation analysis of RAI1 gene.

- Retinal diseases: macular degeneration, retinitis pigmentosa, diabetes, cataracts.

- Skin disease: Lupus (lupus erythematosis), history of skin cancer, history of adverse
reaction(s) to sun (rash, reddening).

- Medications that are photosensitizing: Phenothiazines (Thorazine, Stelazine),
Imipramine (AD), Porphyrins (antitumor), Chloroquine (antimalarial),
Hydrocholorthiazine (antihypertensive, diuretic), Lithium (mood stabilizer) and/or
antibiotics (Tetracycline).

- SMS subjects with extensive medication use may be excluded, depending on medications
used and whether or not discontinuing medications for the trial presents a significant
health risk. These include medications that might affect daytime vigilance (e.g., some
seratonin antagonists such as Trazadone, SSRIs) and/or MAOIs, and/or antipsychotics
(Risperidone), and/or some SSRIs (e.g., fluvoxamine) that affect the metabolism of
melatonin and/or are strong CYP1A2 inhibitors.

Healthy Adult Controls:

- Individuals who have been diagnosed with a sleep disorder (e.g, restless legs, sleep
apnea) known to impact sleep may be excluded at the discretion of the PI.

- Not willing to discontinue caffeine consumption (chocolate, coffee, tea) during study
period.

- Persons with extensive medication use may be excluded, depending on medications used
and whether or not discontinuing medications for the trial presents a significant
health risk. These include medications that might affect daytime vigilance (e.g., some
seratonin antagonists such as Trazadone, SSRIs) and/or MAOIs, and/or antipsychotics
(Risperidone), and/or some SSRIs (e.g., fluvoxamine) that affect the metabolism of
melatonin and/or are strong CYP1A2 inhibitors.

- Employed on a shift work schedule.

- Transmeridian travel within the last 2 weeks.

- Currently using melatonin.

- Women currently taking oral contraceptives (BCPs)

- Pregnant women and/or nursing mothers



Age minimum: 3 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Sleep Disorders, Circadian Rhythm

Mental Retardation

Chromosome Deletion

Self Injurious Behavior

Developmental Delay Disorders

Intervention(s)

Device: Phototherapy (Bright Light)

Drug: dTR Melatonin (NIH CC PDS)

Drug: Melatonin CR

Primary Outcome(s)

Change in level of melatonin (pg/ml) from baseline

Secondary Outcome(s)

Improved sleep parameters (actigraphy). Increased daytime vigilance. Decreased maladaptive behaviors.

Secondary ID(s)

07-HG-0076

070076

Source(s) of Monetary Support

Please refer to primary and secondary sponsors