Melatonin Dose-effect Relation in Childhood Autism

Childhood Autism Clinical Trial

— MELADOSE  

Official title:

Melatonin Dose-effect Relation in Childhood Autism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780883
• Other study ID #: ANSM A91245-56
• Status: Completed
• Phase: Phase 2
• Start date: February 2013
• Est. completion date: September 2013

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: September 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 8 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autistic Disorder
• Childhood Autism

Intervention

Drug:
• melatonin

• Placebo
Placebo tablets of Circadin®

Locations

Country	Name	City	State
France	Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière	Paris
France	Centre Hospitalier Spécialisé Henri Laborit	Poitiers
France	Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré	Reims
France	Pôle de Psychiatrie de l'Enfant et de l'Adolescent - Centre Hospitalier Guillaume Régnier	Rennes

Sponsors (2)

Lead Sponsor	Collaborator
Rennes University Hospital	Centre Hospitalier Guillaume Régnier, RENNES

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severity of autistic disorder		6 weeks after the beginning of the treatment.
Secondary	Severity of autistic impairments	Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ADOS (Autism Diagnostic Observation Scale)	3 weeks after the beginning of the treatment
Secondary	Sleep problems	Sleep problems will be assessed using a parental questionnaire and an actimetry sensor in the child recording	3 weeks after the beginning of the treatment
Secondary	Excretion of the urinary metabolite of melatonin	Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)	3 weeks after the beginning of the treatment
Secondary	Severity of autistic impairments	Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale	3 weeks after the beginning of the treatment
Secondary	Severity of autistic impairments	Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ADOS (Autism Diagnostic Observation Scale)	6 weeks after the beginning of the treatment
Secondary	Sleep problems	Sleep problems will be assessed using a parental questionnaire and an actimetry sensor in the child recording	6 weeks after the beginning of the treatment
Secondary	Excretion of the urinary metabolite of melatonin	Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)	6 weeks after the beginning of the treatment
Secondary	Severity of autistic impairments	Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale	6 weeks after the beginning of the treatment