Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?

Autism Spectrum Disorder Clinical Trial

Official title:

Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02878499
• Other study ID #: 5060
• Status: Recruiting
• Phase: N/A
• Start date: December 19, 2012
• Est. completion date: February 2023

Study information

• Verified date: June 2022
• Source: University Hospital, Strasbourg, France
• Contact: Carmen SCHRODER, MD,PhD
• Phone: 3 88 11 62 18
• Email: schroderc[@]unistra.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to undertake a longitudinal investigation of the impact of sleep and circadian rhythm disturbances on cognitive and behavioural trajectories in children with autism spectrum disorder (ASD) age 3-10 years old.

This innovative study will use objective quantifiable measures of sleep and circadian rhythms in addition to subjective measures.

The investigators aim to assess the hypotheses that, in pre-pubertal children with ASD,

1. sleep disturbances are correlated with circadian rhythm disturbances;

2. both sleep and circadian rhythm disturbances are negatively correlated with cognitive performance and positively correlated with behavioural disturbances;

3. sleep and circadian rhythm disturbances, most notably abnormal melatonin secretion, impact the cognitive and behavioural development of children with ASD, depending on age (prospective longitudinal analyses).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: February 2023
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 8 Years

Eligibility

Inclusion criteria:

• Age: from 3 to 8 years of age at inclusion, as per defined entry ages (longitudinal accelerated design)

• Diagnostic criteria of autism spectrum disorder (ASD)

• Autism Diagnostic Interview (ADI) - revised (R) score compatible with ASD diagnosis

• Autism Diagnostic Observation Schedule (ADOS) score compatible with ASD diagnosis

• Study information has been understood

• Study consent signed by both parents or legal representatives and by the child if the child is capable of expressing his consent

• Stable medication over the 2 months-period preceding inclusion and during evaluation periods (exception: (1) medication mentioned in the exclusion criteria, (2) a new medication instaurated between two evaluation periods is not in itself an exclusion criteria, but will be taken into account in data analysis)

• Compliance with study procedures

• Priori clinical medical examination

• Child affiliated with social security Concerning sleep disorders: the discovery of a primary sleep disorder (e.g.: sleep apnea syndrome, restless legs syndrome, periodic limb movements during sleep) as well as their treatment is not a criteria for terminating the study but will be taken into account in data analysis

Exclusion criteria:

• Secondary autism: e.g. associated with Rett syndrome, fragile X syndrome, Down syndrome, Bourneville tuberous sclerosis, von Recklinghausen disorder, Cytomegalovirus (CMV) encephalitis, congenital rubeola, phenylketonuria.

• Current treatment with melatonin or melatonin agonists before study entry (before baseline assessment)

• Changes in medication over the 2 months-period preceding the study (exception: a new medication instaurated between two evaluation periods is not in itself an exclusion criteria, but will be taken into account in data analysis)

• Transmeridian travel (> 2 time zones) in the month preceding the study

• Participation in other research studies in the 3 months period preceding the study

• Treatment with betablockers, local or systemic non-steroidal anti-inflammatory (NSAI) agents, benzodiazepines, antidepressants

• Severe other intercurrent disorder.

• Severe allergies.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder

Intervention

Other:
• polysomnography

Locations

Country	Name	City	State
France	CHRU de Lille - Hôpital Roger Salengro	Lille
France	CHU de Lyon - CHS Le Vinatier	Lyon
France	CHU Gui de Chaulhiac	Montpellier
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	CHU de TOURS - Hôpital Bretonneau	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline	Sleep latency derived from actigraphy	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in sleep fragmentation index at 1 year follow-up and 2 year follow-up compared to baseline	Sleep fragmentation index derived from polysomnography (PSG)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in nocturnal melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline	Nocturnal melatonin secretion (6-SMT measured in night urine from 8pm to 8am)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in amplitude of the day-night melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline	Amplitude of the day-night melatonin secretion (6 sulfatoxy-melatonin (6-SMT) measured in 12h-night versus 12h-day urine)	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in non-verbal index (INV, derived from the Kaufmann-Assessment Battery fir Children II (K-ABC II)) at 1 year follow-up and 2 year follow-up compared to baseline		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in verbal intelligence quotient (IQ) at 1 year follow-up and 2 year follow-up compared to baseline	Change in verbal intelligence quotient (IQ) derived from the appropriate Wechsler scales for children (WPPSI or WISC) at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in Raven performance IQ at 1 year follow-up and 2 year follow-up compared to baseline	Raven performance IQ derived from Raven progressive matrices (CPM-BF) at 1 year follow-up and 2 year follow-up compared to baseline	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in Autism Diagnostic Observation Schedule (ADOS), module 1-3: part 'D' et 'E' (repetitive and abnormal behaviour) at 1 year follow-up and 2 year follow-up compared to baseline		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Primary	Change in aberrant Behaviour Checklist (ABCL) global score at 1 year follow-up and 2 year follow-up compared to baseline		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	presence of an intrinsic sleep disorders (e.g. obstructive or central sleep apnea syndrome, restless legs syndrome and periodic limb movements during sleep…)		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Total sleep time (TST)		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Time and percentage of TST spent in different sleep stages (slow wave sleep, rapid eye movement (REM) sleep)		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Sleep spindle density in light slow wave sleep		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Density of rapid eye movements in REM sleep		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Spectral analysis of the sleep electro-encephalogram (EEG)		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	24h urinary 6-sulfatoxymelatonin levels (ng/ml)		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Inter-daily stability (IS) and intra-daily variability (IV) of circadian rhythms (actigraphy derived)	Level of ferritin in plasma	Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Circadian phase of body temperature		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary	Level of ferritin in plasma		Three annual assessments: baseline, 1 year follow-up, 2 year follow-up