Does Melatonin Restore Sleep Architecture in Autistic Children

Study Overview
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Brief Summary
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Although behavioral disorders origins in autistic children are still unclear, they seem to be influenced by sleep disorders. Results of studies performed on sleep quality in autistic children showed a high prevalence of sleep disorders in these children, estimated between 50 and 80% compared to children with typical development and insomnia is one of the sleep disorders most frequently reported by autistic children's parents. Others studies showed circadian rhythm disorder in autistic children which could be the consequence of genetic abnormalities in the melatonin synthesis and the melatonin role in the synaptic transmission modulation. Melatonin by its sedative effects and its action on circadian pacemaker is a promoter of sleep proposed for insomnia treatment and circadian rhythm disorders. Two major recent studies (not yet published) in the United States and in England seek to show the effectiveness of melatonin by testing the effects of three doses of melatonin on reducing sleep disorders. It is therefore interesting and important to conduct a parallel study to assess the melatonin effect not only on the reduction of sleep disorders (sleep onset latency, total sleep time…), but on sleep quality (number of nocturnal awakenings). The strength of this study lies in the combination of several measurement tools to assess the melatonin dose-effect on all parameters in both physiological (actimetrics, polysomnography), biological (dosage 24h sulfatoxymelatonin), behavioral (sleep questionnaire, index of insomnia severity, rating scale autistic disorder) as well as possible side effects. The primary objective is to determine the most effective dose of melatonin to improve sleep quality in autistic children.

Official Title
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Does Melatonin Restore Sleep Architecture in Autistic Children?

Conditions
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Sleep Disorders

Intervention / Treatment
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* Drug: melatonin
* Drug: Melatonin
* Drug: Melatonin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Boys and girls from 3 to 12 years old with autism spectrum, Diagnosed by psychiatrists according to the diagnostic criteria for autism ICD-10 AND ADI or ADOS positive, With trouble sleeping, assessed by questionnaire CHSQ, Having made a night polysomnography, Written informed consent (signed by parents), Affiliated with the French universal healthcare system. Exclusion Criteria: Children who stopped all treatment for sleep for less than one month, Liver or kidney insufficiencies, Acute illness during or occurred in the month preceding the study, Neurological disease without autism spectrum , patients with non-controlled epilepsy Health background witch can influence sleep (other than autism itself), Obstructive syndrome (history - oral breathing in wakefulness, nocturnal snoring significant (heard the door closed), nocturnal respiratory effort, apnea reported by parents- and clinical examination (chronic nasal congestion, large tonsils and touching), Known hypersensitivity to the active substance or to one of the excipient contained in the verum or in the placebo, Children under treatment against-indicated with the study treatment witch can't be stopped

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: melatonin 0.5mg<br> | Drug: melatonin<br>* one capsule, melatonin 0.5 mg, oral, once a day, 30 minutes before bedtime<br>|
| Active Comparator: melatonin 2mg<br> | Drug: Melatonin<br>* one capsule, melatonin 2 mg, oral, once a day, 30 minutes before bedtime<br>|
| Active Comparator: melatonin 6mg<br> | Drug: Melatonin<br>* one capsule, melatonin 6 mg, oral, once a day, 30 minutes before bedtime<br>|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* one capsule, placebo, oral, once a day, 30 minutes before bedtime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the most effective dose of melatonin to improve sleep quality in autistic children. | The primary outcome is to measure the awakenings index which is the number of nocturnal awakenings higher than 15 seconds per hour of sleep measured by polysomnography. | The primary outcome will be assessed once at V2 (D29 +/- 7days) by polysomnography. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess in autistic children the melatonin effects on sleep characteristics | by measuring the sleep latency | It will be assessed once at V2 (D29 +/- 7 days) by polysomnography and actimetrics. | 
| To assess the effectiveness of treatment on sleep disorders. | It is to evaluate the effectiveness with the scale treatment response, the sleep questionnaire and severity index of insomnia | It will be assessed once at V2 (D29 +/- 7 days) by polysomnography and actimetrics. | 
| To assess the effectiveness of melatonin on daytime autistic behavior | Evaluate the effectiveness with the rating scale autistic behavior. | It will be assessed three times at V1 (D0), V2 (D29 +/- 7 days) and V4 (D44+/-7days). | 
| To assess the melatonin safety in autistic children. | Evaluate the safety with Adverse events report. | It will be assessed three times at V2 (D29 +/- 7 days), V3(D30) and V4 (D44+/-7days). | 
| Establish whether there is a correlation between sleep quality and melatonin secretion. | With the urinary melatonin dosage. | It will be assessed twice at V3 (D30) and V4 (D44+/-7days). | 
| To assess in autistic children the melatonin effects on sleep characteristics. | by measuring the indexes arousals | at V2 (D29 +/- 7 days) by polysomnography and actimetrics. | 
| To assess in autistic children the melatonin effects on sleep characteristics. | by measuring time and percentage of different stages of NREM (Non rapid eye movement) and REM sleep | at V2 (D29 +/- 7 days) by polysomnography and actimetrics. | 
| To assess in autistic children the melatonin effects on sleep characteristics | by measuring the density of sleep spindles in light NREM sleep | at V2 (D29 +/- 7 days) by polysomnography and actimetrics | 
| To assess in autistic children the melatonin effects on sleep characteristics | by measuring the density of eye movements REM sleep. | at V2 (D29 +/- 7 days) by polysomnography and actimetrics. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep,melatonin,autism,children