MELADOSE: Melatonin Dose-effect Relation in Childhood Autism

Sponsor

Rennes University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01780883

Collaborator

Centre Hospitalier Guillaume Régnier, RENNES (Other)

Enrollment

Locations

Arms

Duration (Months)

8.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Autism	Drug: melatonin Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Melatonin Dose-effect Relation in Childhood Autism

Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo 5 tablets of placebo once a day, an hour before falling asleep, for 6 weeks.	Drug: Placebo Placebo tablets of Circadin®
Experimental: 2 mg melatonin 1 tablet of 2mg melatonin and 4 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.	Drug: melatonin Other Names: Circadin® Drug: Placebo Placebo tablets of Circadin®
Experimental: 4 mg melatonin 2 tablets of 2mg melatonin and 3 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.	Drug: melatonin Other Names: Circadin® Drug: Placebo Placebo tablets of Circadin®
Experimental: 10 mg melatonin 5 tablets of 2mg melatonin once a day, an hour before falling asleep, for 6 weeks.	Drug: melatonin Other Names: Circadin®

Outcome Measures

Primary Outcome Measures

Severity of autistic disorder [6 weeks after the beginning of the treatment.]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 8 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière	Paris	France	75013
2	Centre Hospitalier Spécialisé Henri Laborit	Poitiers	France	86280
3	Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré	Reims	France	51092
4	Pôle de Psychiatrie de l'Enfant et de l'Adolescent - Centre Hospitalier Guillaume Régnier	Rennes	France	35200

Sponsors and Collaborators

Rennes University Hospital
Centre Hospitalier Guillaume Régnier, RENNES

Investigators

Principal Investigator: Sylvie TORDJMAN, MD, PhD, Centre Hospitalier Guillaume Régnier, RENNES
Study Chair: Eric BELLISSANT, MD, PhD, Rennes University Hospital