Clinical trial NCT01780883: Melatonin Dose-effect Relation in Childhood Autism
Official title: Melatonin Dose-effect Relation in Childhood Autism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Childhood Autism
Keywords: melatonin
childhood autism
6-Sulphatoxymelatonin
autistic disorder
dose-effect relation
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Guillaume Régnier, RENNES
First posted: 2013-01-31
Enrollment: 34
Sex: MALE
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Melatonin is a neurohormone produced from serotonin which promotes sleep. The alterations in central and peripheral serotonin neurobiology and in circadian sleep-wake rhythms observed in autistic disorder suggest abnormalities in melatonin secretion.

Several studies have reported a decrease in melatonin secretion in individuals with autism. Furthermore, nocturnal excretion of 6-Sulphatoxymelatonin (the predominant melatonin metabolite) was significantly negatively correlated with severity of autistic impairments in verbal communication and play. Melatonin could therefore have a therapeutic effect on sleep problems and may play a role in the pathophysiology of autistic disorder.

These data highlight the possible therapeutic interest of an oral administration of melatonin in patients with autistic disorder. Thus, the objective of this clinical trial is to study the relation between the melatonin dose administered and its effect on severity of autistic impairments especially in verbal communication and play.

Detailed description: The hormone melatonin is of interest in autism due to theoretical considerations and reports of altered melatonin production in individuals with autism. Melatonin produced in the pineal gland helps regulate human circadian rhythms including sleep-wake, and is considered as the best measure of circadian rhythms.

Several studies revealed that plasmatic and urinary nocturnal levels of melatonin are significantly lower in individuals with autism (in particular, in prepubertal children) compared to typically developing individuals. In addition, this reduction in nocturnal melatonin was significantly associated with the severity of communication and social interaction impairments, especially in verbal communication and play. Finally, diurnal excretion of melatonin was also found to be decreased in individuals with autistic disorder.

Given these results, administration of melatonin could serve, at least in prepubertal children wih autism, to normalize physiological, developmental and behavioral processes that are influenced by this pineal hormone. A randomized clinical trial is therefore necessary to establish potential therapeutic efficacy of melatonin in autistic disorder and to specify its dose-effect relation. This is the first clinical trial studying the melatonin dose-effect in autism.

Eligibility criteria: Inclusion Criteria:

* Prepubertal males with autism from 6 to 8 years old, according to the diagnostic criteria of autistic disorder of the WHO (CIM-10), American (DSM-IV-TR) and French (CFTMEA) classifications.
* Verbal language level required for the ADOS (Module 1) (i.e., no verbal language as defined by the ADI-R (autism diagnostic interview-revised) scale).
* Written informed consent of the parents or the legal representative.

Non-inclusion Criteria:

* Treatment by benzodiazepines.
* Treatment by anticonvulsant drugs.
* Treatment by serotoninergic products.
* Hypersensitivity reaction to the active substance or one of the excipients of the product.
* Patient with hereditary galactose intolerance, Lapp lactase deficiency or malabsorption syndrome of glucose and galactose.
* Children who are not able to swallow tablets.

Primary outcomes:
measure: Severity of autistic disorder
timeFrame: 6 weeks after the beginning of the treatment.
Secondary outcomes:
measure: Severity of autistic impairments
timeFrame: 3 weeks after the beginning of the treatment
measure: Sleep problems
timeFrame: 3 weeks after the beginning of the treatment
measure: Excretion of the urinary metabolite of melatonin
timeFrame: 3 weeks after the beginning of the treatment
measure: Severity of autistic impairments
timeFrame: 3 weeks after the beginning of the treatment
measure: Severity of autistic impairments
timeFrame: 6 weeks after the beginning of the treatment
measure: Sleep problems
timeFrame: 6 weeks after the beginning of the treatment
measure: Excretion of the urinary metabolite of melatonin
timeFrame: 6 weeks after the beginning of the treatment
measure: Severity of autistic impairments
timeFrame: 6 weeks after the beginning of the treatment
Other outcomes:
Locations:
city: Paris
country: France
facility: Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière
city: Poitiers
country: France
facility: Centre Hospitalier Spécialisé Henri Laborit
city: Reims
country: France
facility: Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré
city: Rennes
country: France
facility: Pôle de Psychiatrie de l'Enfant et de l'Adolescent - Centre Hospitalier Guillaume Régnier
Study officials:
affiliation: Centre Hospitalier Guillaume Régnier, RENNES
name: Sylvie TORDJMAN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rennes University Hospital
name: Eric BELLISSANT, MD, PhD
role: STUDY_CHAIR
References:
citation: Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N, Fougerou C. Melatonin: Pharmacology, Functions and Therapeutic Benefits. Curr Neuropharmacol. 2017 Apr;15(3):434-443. doi: 10.2174/1570159X14666161228122115.