Melatonin Dose-effect Relation in Childhood Autism

NCT ID: NCT01780883

Last Updated: 2025-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2013-09-30

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.

Conditions

Childhood Autism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

5 tablets of placebo once a day, an hour before falling asleep, for 6 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets of Circadin®

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.

Group Type: EXPERIMENTAL

melatonin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo tablets of Circadin®

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.

Group Type: EXPERIMENTAL

melatonin

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo tablets of Circadin®

10 mg melatonin

5 tablets of 2mg melatonin once a day, an hour before falling asleep, for 6 weeks.

Group Type: EXPERIMENTAL

melatonin

Intervention Type: DRUG

Interventions

melatonin

Intervention Type: DRUG

Placebo

Placebo tablets of Circadin®

Intervention Type: DRUG

Other Intervention Names

Circadin®

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.

• 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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 8 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Guillaume Régnier, RENNES

UNKNOWN

Sponsor Role: collaborator

Rennes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sylvie TORDJMAN, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Guillaume Régnier, RENNES

Eric BELLISSANT, MD, PhD

Role: STUDY_CHAIR

Rennes University Hospital

Locations

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, , France

Countries

France

References

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.

Reference Type: RESULT

PMID: 28503116 (View on PubMed)

Other Identifiers

ANSM A91245-56

Identifier Type: -

Identifier Source: org_study_id