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

This study is currently recruiting participants.
Verified August 2016 by University Hospital, Strasbourg, France
Sponsor:
ClinicalTrials.gov Identifier:
NCT02878499
First Posted: August 25, 2016
Last Update Posted: August 25, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
University Hospital, Strasbourg, France
  Purpose

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).

Condition Intervention
Autism Spectrum Disorder Other: polysomnography

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?

Resource links provided by NLM:


Further study details as provided by University Hospital, Strasbourg, France:

Primary Outcome Measures:
  • Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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…) [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
  • Total sleep time (TST) [ Time Frame: 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) [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
  • Sleep spindle density in light slow wave sleep [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
  • Density of rapid eye movements in REM sleep [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
  • Spectral analysis of the sleep electro-encephalogram (EEG) [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
  • 24h urinary 6-sulfatoxymelatonin levels (ng/ml) [ Time Frame: 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) [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
    Level of ferritin in plasma

  • Circadian phase of body temperature [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]
  • Level of ferritin in plasma [ Time Frame: Three annual assessments: baseline, 1 year follow-up, 2 year follow-up ]

Estimated Enrollment: 105
Study Start Date: December 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
ASD Other: polysomnography

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02878499


Contacts
Contact: Carmen SCHRODER, MD,PhD 3 88 11 62 18 ext +33 schroderc@unistra.fr

Locations
France
Hôpitaux Universitaires de Strasbourg Recruiting
Strasbourg, France
Contact: Carmen Schröder, MD, PhD    3 88 11 62 18 ext +33    schroderc@unistra.fr   
Sponsors and Collaborators
University Hospital, Strasbourg, France
  More Information

Responsible Party: University Hospital, Strasbourg, France
ClinicalTrials.gov Identifier: NCT02878499     History of Changes
Other Study ID Numbers: 5060
First Submitted: June 14, 2016
First Posted: August 25, 2016
Last Update Posted: August 25, 2016
Last Verified: August 2016

Keywords provided by University Hospital, Strasbourg, France:
autism
autism spectrum disorder
ASD
sleep
Circadian
Biological rhythms
melatonin
Cognition
Behavior
Longitudinal
Longitudinal accelerated design

Additional relevant MeSH terms:
Autistic Disorder
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders