Smith Magenis Syndrome Study

Smith-Magenis Syndrome Clinical Trial

— SMS  

Official title:

Chronobiological Characterization of Smith Magenis Syndrome in Paediatric Age

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05116904
• Other study ID #: 69HCL20_0682
• Status: Recruiting
• Phase: N/A
• Start date: March 30, 2022
• Est. completion date: April 2024

Study information

• Verified date: October 2022
• Source: Hospices Civils de Lyon
• Contact: Patricia FRANCO, Pr
• Phone: 0427856052
• Email: patricia.franco[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Smith Magenis Syndrome (SMS) is a complex disorder characterized by severe neurological, psychological and behavioral disorders including sleep-wake rhythm disorders. It is a rare disease with a prevalence of 1/25 000. The sleep disorders observed could be the consequence of a general dysregulation of the circadian system, since these patients show an inversion of the melatonin secretion profile. In SMS, the peak of melatonin is observed at 12 o'clock, whereas it is nocturnal in healthy subjects (3-4 o'clock in the morning). Daylight plays a important role in circadian regulation by inducing an inhibition of melatonin secretion via the suprachiasmatic nuclei of the hypothalamus. This mechanism could be affected in SMS children, explaining the lag of melatonin profile. These sleep-wake disturbances cycle could play a significant role in learning deficits and in the frequency and severity of behavioral abnormalities observed in SMS. In this project, investigators propose to study the mechanisms involved in the sleep-wake cycle disorders observed in Smith Magenis children, in particular by evaluating the quality of the pupillary reflex using a pupillometer. The pupillary reflex is a simple and non-invasive method to test light sensitivity and the photobiological mechanisms involved. In this way, investigators want to evaluate the diurnal profile of the pupillary reflex in children with Smith Magenis syndrome in relation to the diurnal melatonin profile. Investigators will complete this study by determining the chronobiological profile of Smith Magenis patients by measuring different variables: - Diurnal cortisol and amylase profile - 24h body temperature and heart rate profile - Urinary cortisol and 6-sulfatoxymelatonin (major metabolite of melatonin) profiles - Daytime sleepiness profile measured subjectively by questionnaire and objectively via a waking EEG recording. - Actimetry at home - Polysomnography - A neurocognitive and behavioural assessment

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 12 Years

Eligibility

Inclusion Criteria:

• Genetically confirmed Smith Magenis syndrome (microdeletion of the short arm of chromosome 17 or mutation of the RAI1 gene; obtained by FISH, CGH-array or molecular biology)
• Aged 7-12 years
• Consent form signed by the parent(s)
• Requiring a sleep assessment in the Hopital Femme Mère Enfant paediatric sleep unit of Pr Franco
• Affiliation to a social security system.

Exclusion Criteria:

• Associated ophthalmological disorders that do not allow the photomotor reflex to be studied: optic neuritis, glaucoma and retinitis pigmentosa.
• Dyschromatopsia detected in consultation with a rapid Ishihara test adapted to the child's cognitive level, if necessary supplemented by a test performed by ophthalmologists.
• Algic child (risk of measurement bias: when a patient is in pain his pupils dilate and we observe a greater amplitude in the photomotor reflex), defined by a score on the FPS-R Face Scale >4/10.

Related Conditions & MeSH terms

• Smith-Magenis Syndrome
• Syndrome

Intervention

Other:
• Assessment
Pupil reflex and melatonin profile, circadian profile assessment

Locations

Country	Name	City	State
France	Ge´noPsy, Reference Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier and EDR-Psy Q19 Team (Centre National de la Recherche Scientifique & Lyon 1 Claude Bernard University)	Bron
France	Service Épilepsie-Sommeil-Explorations Fonctionnelles Neurologiques Pédiatriques Hôpital Femme-Mère-Enfant HCL	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measurement of the percentage change between pupil diameter at the end of light exposure and before exposure	This measurement will allow to evaluate the diurnal profile of the pupillary reflex and will be measured by a NeuroLight pupillometer (IDMed).; This measurement will be done every 2 hours from 8am to 8pm, for one day	One day
Primary	Measurement of salivary melatonin levels	This measurement will allow to evaluate the diurnal melatonin profile and will be evaluated using saliva samples.; This measurement will be done every 2 hours from 8am to 8pm, for one day	One day
Secondary	Determination of the chronobiological profile : Salivary cortisol levels	Salivary cortisol levels will be evaluated using saliva samples	Every 2 hours from 8am to 8pm, for one day
Secondary	Determination of the chronobiological profile : Amylase levels	Amylase levels will be evaluated using saliva samples	Every 2 hours from 8am to 8pm, for one day
Secondary	Determination of the chronobiological profile : Urinary 6-sulfatoxymelatonin level	Urinary 6-sulfatoxymelatonin level will be evaluated using urinary samples	over 24hours
Secondary	Determination of the chronobiological profile : Urinary cortisol level	Urinary cortisol level will be evaluated using urinary samples	over 24hours
Secondary	Determination of the chronobiological profile : Variations in body temperature in degrees	Body temperature will be measured by ibuttonR placed on the surface of the skin	over 24hours
Secondary	Determination of the chronobiological profile : Assessment of sleepiness by questionnaire (numerical score)	The Karolinska questionnaire will be carried out at the time of salivary sampling and pupil diameter measurement and the score obtained will be compared with the salivary melatonin level.	Every 2 hours from 8am to 8pm, for one day
Secondary	Determination of the chronobiological profile : Assessment of sleepiness by spectral analysis (EEG)	Somnolence will be evaluated by calculating power spectrum in several frequency bands.	Every 2 hours from 8am to 8pm, for one day
Secondary	Determination of the chronobiological profile : Sleep assessment by actimetry	Home activity monitor during an outpatient recording with a watch in order to assess the sleep wake rhythm at home	2 weeks
Secondary	Determination of the chronobiological profile :Sleep assessment by Polysomnography	Polysomnography during hospitalization in order to assess the structure of sleep	24 hours
Secondary	Neuropsychological assessment	WISC +/- Vineland	One day