Smith Magenis Syndrome and Autism Spectrum Disorders

NCT05116904 | Recruiting

• 1 other identifier: 69HCL20_0682
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Autism Spectrum Disorders (ASD) are a neurodevelopmental disorder. Their prevalence is estimated at around 0.4% of the general population worldwide. Their early onset and chronic nature make them a disabling disorder, all the more so as there is a high prevalence of sleep disorders in these populations, estimated at between 50 and 80%, with many complaints of insomnia in particular. These sleep disorders may result from biological, psychological, social, environmental and family factors. 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. These sleep disorders observed could be the consequence of a general dysregulation of the circadian system, since SMS patients show an inversion of the melatonin secretion profile (with a totally abnormal diurnal peak) and in patients with autism spectrum disorders, an overall reduction in melatonin secretion. 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 and ASD. In this project, investigators propose to study the mechanisms involved in the sleep-wake cycle disorders observed in Smith Magenis and Autism Spectrum 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 and with Autism Spectrum Disorders in relation to the diurnal melatonin profile. Investigators will complete this study by determining the chronobiological profile of these 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

Conditions

Smith-Magenis Syndrome; Autism Spectrum Disorder

Keywords

Sleep disorders; Chronobiology; Smith Magenis Syndrome; Paediatrics; Pupillary reflex; Circadian rhythm; Melatonin; Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• Determination of the chronobiological profile : Salivary cortisol levels

  Every 2 hours from 8am to 8pm, for one day

• Determination of the chronobiological profile : Amylase levels

  Every 2 hours from 8am to 8pm, for one day

• Determination of the chronobiological profile : Urinary 6-sulfatoxymelatonin level

  over 24hours

• Determination of the chronobiological profile : Urinary cortisol level

  over 24hours

• Determination of the chronobiological profile : Variations in body temperature in degrees

  over 24hours

Study Arms (2)

Children with Smith Magenis Syndrome

OTHER

Other: Assessment

Children with Autism Spectrum Disorders

OTHER

Other: Assessment

Interventions

Assessment OTHER

Pupil reflex and melatonin profile, circadian profile assessment

Children with Autism Spectrum Disorders; Children with Smith Magenis Syndrome

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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) and children with neuropsychologically confirmed autism spectrum disorder, with no genetic pathology found.
• Aged 5-12 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.

You may not qualify if:

• Associated ophthalmological disorders that do not allow the photomotor reflex to be studied: optic neuritis, glaucoma and retinitis pigmentosa.
• 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.
• Only for SMS patients:
• \- 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (2)

Service Épilepsie-Sommeil-Explorations Fonctionnelles Neurologiques Pédiatriques Hôpital Femme-Mère-Enfant HCL

Bron, 69677, France

RECRUITING

GénoPsy, 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, 69678, France

RECRUITING

MeSH Terms

Conditions

Smith-Magenis Syndrome; Autism Spectrum Disorder; Sleep Wake Disorders

Interventions

Restraint, Physical

Condition Hierarchy (Ancestors)

Chronobiology Disorders; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Behavior Control; Therapeutics; Immobilization; Investigative Techniques

Study Officials

• Patricia FRANCO, PhD

  Service Épilepsie-Sommeil-Explorations Fonctionnelles Neurologiques Pédiatriques, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patricia FRANCO, PhD

CONTACT

0427856052; patricia.franco@chu-lyon.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2021
• First Posted: November 11, 2021
• Study Start: March 30, 2022
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: June 6, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)