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

NCT02878499 | Unknown

• 1 other identifier: 5060
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 5

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. 1.sleep disturbances are correlated with circadian rhythm disturbances;
2. 2.both sleep and circadian rhythm disturbances are negatively correlated with cognitive performance and positively correlated with behavioural disturbances;
3. 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).

Conditions

Autism Spectrum Disorder

Keywords

autism; autism spectrum disorder; ASD; sleep; Circadian; Biological rhythms; melatonin; Cognition; Behavior; Longitudinal; Longitudinal accelerated design

Outcome Measures

Primary Outcomes (9)

• 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

• 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

• 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

• 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

• 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

  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

• 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

• 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 Outcomes (10)

• 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

Study Arms (1)

ASD

OTHER

Other: polysomnography

Interventions

polysomnography OTHER

ASD

Eligibility Criteria

• Age: 3 Years - 8 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)
• 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.

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (5)

CHRU de Lille - Hôpital Roger Salengro

Lille, 59037, France

RECRUITING

CHU de Lyon - CHS Le Vinatier

Lyon, 69100, France

RECRUITING

CHU Gui de Chaulhiac

Montpellier, 34295, France

RECRUITING

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

RECRUITING

CHU de TOURS - Hôpital Bretonneau

Tours, 37044, France

RECRUITING

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder; Behavior

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Central Study Contacts

Carmen SCHRODER, MD,PhD

CONTACT

3 88 11 62 18; schroderc@unistra.fr

Study Design

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

Study Record Dates

• First Submitted: June 14, 2016
• First Posted: August 25, 2016
• Study Start: December 19, 2012
• Primary Completion: December 1, 2022
• Study Completion: February 1, 2023
• Last Updated: June 30, 2022

Record last verified: 2022-06

Locations

FR (5)