Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 105
- 试验地点
- 10
- 主要终点
- Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline
研究概览
简要总结
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,
- sleep disturbances are correlated with circadian rhythm disturbances;
- both sleep and circadian rhythm disturbances are negatively correlated with cognitive performance and positively correlated with behavioural disturbances;
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 8 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •, (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.
结局指标
主要结局
Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline
时间窗: 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
时间窗: 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
时间窗: 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 aberrant Behaviour Checklist (ABCL) global score at 1 year follow-up and 2 year follow-up compared to baseline
时间窗: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Change in amplitude of the day-night melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline
时间窗: 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
时间窗: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Change in Raven performance IQ at 1 year follow-up and 2 year follow-up compared to baseline
时间窗: 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
时间窗: 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
时间窗: 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
次要结局
- Sleep spindle density in light slow wave 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)
- 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)
- Level of ferritin in plasma(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)
- 24h urinary 6-sulfatoxymelatonin levels (ng/ml)(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)
- 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)
- Circadian phase of body temperature(Three annual assessments: baseline, 1 year follow-up, 2 year follow-up)