Does Melatonin Restore Sleep Architecture in Autistic Children (SOMELIA)

Does Melatonin Restore Sleep Architecture in Autistic Children?

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.

Study Overview

• Status: Completed
• Conditions: Sleep Disorders
• Intervention / Treatment: Drug: melatonin; Drug: Melatonin; Drug: Melatonin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hopital Femme Mere Enfant
  • Caen, France, 14033
    • CHU de Caen
  • Chinon, France
    • Centre Hospitalier du Chinonais
  • Strasbourg, France, 67091
    • CHRU de Strasbourg
  • Tours, France, 37044
    • CHU de Tours

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Patricia Franco, MD, CHU Hôpital Femme Mère Enfant.Bron

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): June 12, 2018
• Study Completion (Actual): June 12, 2018

Study Registration Dates

• First Submitted: November 13, 2013
• First Submitted That Met QC Criteria: November 19, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): January 28, 2019
• Last Update Submitted That Met QC Criteria: January 25, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: sleep,melatonin,autism,children
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Sleep Wake Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 2012-732; 2013-001230-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No