Back to resultsDo Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?
Primary Purpose
Autism Spectrum Disorder
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
polysomnography
Sponsored by
About this trial
This is an interventional other trial for Autism Spectrum Disorder focused on measuring autism, autism spectrum disorder, ASD, sleep, Circadian, Biological rhythms, melatonin, Cognition, Behavior, Longitudinal, Longitudinal accelerated design
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.
Sites / Locations
- CHRU de Lille - Hôpital Roger SalengroRecruiting
- CHU de Lyon - CHS Le VinatierRecruiting
- CHU Gui de ChaulhiacRecruiting
- Hôpitaux Universitaires de StrasbourgRecruiting
- CHU de TOURS - Hôpital BretonneauRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
ASD
Arm Description
Outcomes
Primary Outcome Measures
Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline
Sleep latency derived from actigraphy
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)
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)
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)
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
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
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
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
Change in aberrant Behaviour Checklist (ABCL) global score at 1 year follow-up and 2 year follow-up compared to baseline
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…)
Total sleep time (TST)
Time and percentage of TST spent in different sleep stages (slow wave sleep, rapid eye movement (REM) sleep)
Sleep spindle density in light slow wave sleep
Density of rapid eye movements in REM sleep
Spectral analysis of the sleep electro-encephalogram (EEG)
24h urinary 6-sulfatoxymelatonin levels (ng/ml)
Inter-daily stability (IS) and intra-daily variability (IV) of circadian rhythms (actigraphy derived)
Level of ferritin in plasma
Circadian phase of body temperature
Level of ferritin in plasma
Full Information
NCT ID
NCT02878499
First Posted
June 14, 2016
Last Updated
June 28, 2022
Sponsor
University Hospital, Strasbourg, France
1. Study Identification
Unique Protocol Identification Number
NCT02878499
Brief Title
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
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2012 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France
4. Oversight
Data Monitoring Committee
No
5. 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,
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder
Keywords
autism, autism spectrum disorder, ASD, sleep, Circadian, Biological rhythms, melatonin, Cognition, Behavior, Longitudinal, Longitudinal accelerated design
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
105 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ASD
Arm Type
Other
Intervention Type
Other
Intervention Name(s)
polysomnography
Primary Outcome Measure Information:
Title
Change in sleep latency at 1 year follow-up and 2 year follow-up compared to baseline
Description
Sleep latency derived from actigraphy
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Change in sleep fragmentation index at 1 year follow-up and 2 year follow-up compared to baseline
Description
Sleep fragmentation index derived from polysomnography (PSG)
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Change in nocturnal melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline
Description
Nocturnal melatonin secretion (6-SMT measured in night urine from 8pm to 8am)
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Change in amplitude of the day-night melatonin secretion at 1 year follow-up and 2 year follow-up compared to baseline
Description
Amplitude of the day-night melatonin secretion (6 sulfatoxy-melatonin (6-SMT) measured in 12h-night versus 12h-day urine)
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
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
Title
Change in verbal intelligence quotient (IQ) at 1 year follow-up and 2 year follow-up compared to baseline
Description
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
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Change in Raven performance IQ at 1 year follow-up and 2 year follow-up compared to baseline
Description
Raven performance IQ derived from Raven progressive matrices (CPM-BF) 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
Title
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
Title
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 Measure Information:
Title
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
Title
Total sleep time (TST)
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
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
Title
Sleep spindle density in light slow wave sleep
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Density of rapid eye movements in REM sleep
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Spectral analysis of the sleep electro-encephalogram (EEG)
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
24h urinary 6-sulfatoxymelatonin levels (ng/ml)
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Inter-daily stability (IS) and intra-daily variability (IV) of circadian rhythms (actigraphy derived)
Description
Level of ferritin in plasma
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Circadian phase of body temperature
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
Title
Level of ferritin in plasma
Time Frame
Three annual assessments: baseline, 1 year follow-up, 2 year follow-up
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carmen SCHRODER, MD,PhD
Phone
3 88 11 62 18
Ext
+33
Email
schroderc@unistra.fr
Facility Information:
Facility Name
CHRU de Lille - Hôpital Roger Salengro
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Louis GOEB, MD
Phone
03 20 44 49 13
Ext
+33
Email
jl-goeb@chru-lille.fr
First Name & Middle Initial & Last Name & Degree
Jean-Louis GOEB, MD
First Name & Middle Initial & Last Name & Degree
Christelle MONACA
Facility Name
CHU de Lyon - CHS Le Vinatier
City
Lyon
ZIP/Postal Code
69100
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas GEORGIEFF
Phone
04 37 91 12 47
Ext
+33
Email
nicolas.georgieff@ch-le-vinatier.fr
First Name & Middle Initial & Last Name & Degree
Patricia FRANCO
Phone
04 27 85 60 52
Ext
+33
Email
patricia.franco-gillioen@univ-lyon1.fr
First Name & Middle Initial & Last Name & Degree
Nicolas GEORGIEFF
First Name & Middle Initial & Last Name & Degree
Patricia FRANCO
Facility Name
CHU Gui de Chaulhiac
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amaria BAGHDADLI
Phone
04 67 33 99 68
Ext
+33
Email
cent-ress-autisme@chu-montpellier.fr
First Name & Middle Initial & Last Name & Degree
Amaria BAGHDADLI
First Name & Middle Initial & Last Name & Degree
Yves DAUVILLIERS
Facility Name
Hôpitaux Universitaires de Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carmen Schröder, MD, PhD
Phone
3 88 11 62 18
Ext
+33
Email
schroderc@unistra.fr
First Name & Middle Initial & Last Name & Degree
Carmen SCHRÖDER
First Name & Middle Initial & Last Name & Degree
Patrice BOURGIN
Facility Name
CHU de TOURS - Hôpital Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédérique BONNET-BRILHAULT
Phone
02 47 47 84 12
Ext
+33
Email
f.bonnet-brilhault@chu-tours.fr
First Name & Middle Initial & Last Name & Degree
Nadège LIMOUSIN CHAMPFAILLY
Phone
02 47 47 38 25
Ext
+33
Email
N.LIMOUSIN-CHAMPFAILLY@chu-tours.fr
First Name & Middle Initial & Last Name & Degree
Frédérique BONNET-BRILHAULT
First Name & Middle Initial & Last Name & Degree
Nadège LIMOUSIN CHAMPFAILLY
First Name & Middle Initial & Last Name & Degree
Bertrand De TOFFOL
12. IPD Sharing Statement
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Do Sleep and Circadian Rhythm Disturbances Impact the Cognitive and Behavioural Development of Children With Autism?
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