Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?
Study Details
Study Description
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,
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sleep disturbances are correlated with circadian rhythm disturbances;
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both sleep and circadian rhythm disturbances are negatively correlated with cognitive performance and positively correlated with behavioural disturbances;
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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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: ASD
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Other: polysomnography
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Outcome Measures
Primary Outcome Measures
- Change in sleep latency 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]
Sleep latency derived from actigraphy
- Change in sleep fragmentation index 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]
Sleep fragmentation index derived from polysomnography (PSG)
- Change in nocturnal melatonin secretion 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]
Nocturnal melatonin secretion (6-SMT measured in night urine from 8pm to 8am)
- Change in amplitude of the day-night melatonin secretion 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]
Amplitude of the day-night melatonin secretion (6 sulfatoxy-melatonin (6-SMT) measured in 12h-night versus 12h-day urine)
- 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]
- Change in verbal intelligence quotient (IQ) 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]
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
- Change in Raven performance IQ 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]
Raven performance IQ derived from Raven progressive matrices (CPM-BF) at 1 year follow-up and 2 year follow-up compared to baseline
- 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]
- 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 Outcome Measures
- 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]
- Total sleep time (TST) [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
- 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]
- Sleep spindle density in light slow wave sleep [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
- Density of rapid eye movements in REM sleep [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
- Spectral analysis of the sleep electro-encephalogram (EEG) [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
- 24h urinary 6-sulfatoxymelatonin levels (ng/ml) [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
- Inter-daily stability (IS) and intra-daily variability (IV) of circadian rhythms (actigraphy derived) [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
Level of ferritin in plasma
- Circadian phase of body temperature [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
- Level of ferritin in plasma [Three annual assessments: baseline, 1 year follow-up, 2 year follow-up]
Eligibility Criteria
Criteria
Inclusion criteria:
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Age: from 3 to 8 years of age at inclusion, as per defined entry ages (longitudinal accelerated design)
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Diagnostic criteria of autism spectrum disorder (ASD)
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Autism Diagnostic Interview (ADI) - revised (R) score compatible with ASD diagnosis
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Autism Diagnostic Observation Schedule (ADOS) score compatible with ASD diagnosis
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Study information has been understood
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Study consent signed by both parents or legal representatives and by the child if the child is capable of expressing his consent
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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)
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Compliance with study procedures
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Priori clinical medical examination
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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:
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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.
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Current treatment with melatonin or melatonin agonists before study entry (before baseline assessment)
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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)
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Transmeridian travel (> 2 time zones) in the month preceding the study
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Participation in other research studies in the 3 months period preceding the study
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Treatment with betablockers, local or systemic non-steroidal anti-inflammatory (NSAI) agents, benzodiazepines, antidepressants
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Severe other intercurrent disorder.
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Severe allergies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHRU de Lille - Hôpital Roger Salengro | Lille | France | 59037 | |
| 2 | CHU de Lyon - CHS Le Vinatier | Lyon | France | 69100 | |
| 3 | CHU Gui de Chaulhiac | Montpellier | France | 34295 | |
| 4 | Hôpitaux Universitaires de Strasbourg | Strasbourg | France | 67091 | |
| 5 | CHU de TOURS - Hôpital Bretonneau | Tours | France | 37044 |
Sponsors and Collaborators
- University Hospital, Strasbourg, France
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 5060