Clinical trial NCT02878499: Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?
Official title: Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Autism Spectrum Disorder
Keywords: autism
autism spectrum disorder
ASD
sleep
Circadian
Biological rhythms
melatonin
Cognition
Behavior
Longitudinal
Longitudinal accelerated design
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2016-08-25
Enrollment: 105
Sex: ALL
Minimum age (years): 3
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Change in sleep fragmentation index at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Change in nocturnal melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Change in amplitude of the day-night melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: 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
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Change in verbal intelligence quotient (IQ) at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Change in Raven performance IQ at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: 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
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Change in aberrant Behaviour Checklist (ABCL) global score at 1 year follow-up and 2 year follow-up compared to baseline
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Secondary outcomes:
measure: presence of an intrinsic sleep disorders (e.g. obstructive or central sleep apnea syndrome, restless legs syndrome and periodic limb movements during sleep…)
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Total sleep time (TST)
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Time and percentage of TST spent in different sleep stages (slow wave sleep, rapid eye movement (REM) sleep)
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Sleep spindle density in light slow wave sleep
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Density of rapid eye movements in REM sleep
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Spectral analysis of the sleep electro-encephalogram (EEG)
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: 24h urinary 6-sulfatoxymelatonin levels (ng/ml)
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Inter-daily stability (IS) and intra-daily variability (IV) of circadian rhythms (actigraphy derived)
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Circadian phase of body temperature
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
measure: Level of ferritin in plasma
timeFrame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU de Lille - Hôpital Roger Salengro
city: Lyon
country: France
facility: CHU de Lyon - CHS Le Vinatier
city: Montpellier
country: France
facility: CHU Gui de Chaulhiac
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Tours
country: France
facility: CHU de TOURS - Hôpital Bretonneau
Study officials:
References: