Melatonin Dose-effect Relation in Childhood Autism (MELADOSE)

January 17, 2025 updated by: Rennes University Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière
      • Poitiers, France, 86280
        • Centre Hospitalier Spécialisé Henri Laborit
      • Reims, France, 51092
        • Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré
      • Rennes, France, 35200
        • Pôle de Psychiatrie de l'Enfant et de l'Adolescent - Centre Hospitalier Guillaume Régnier

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 4 years (Child)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Severity of autistic disorder
Time Frame: 6 weeks after the beginning of the treatment.
6 weeks after the beginning of the treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of autistic impairments
Time Frame: 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)
3 weeks after the beginning of the treatment
Sleep problems
Time Frame: 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
3 weeks after the beginning of the treatment
Excretion of the urinary metabolite of melatonin
Time Frame: 3 weeks after the beginning of the treatment
Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)
3 weeks after the beginning of the treatment
Severity of autistic impairments
Time Frame: 3 weeks after the beginning of the treatment
Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale
3 weeks after the beginning of the treatment
Severity of autistic impairments
Time Frame: 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)
6 weeks after the beginning of the treatment
Sleep problems
Time Frame: 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
6 weeks after the beginning of the treatment
Excretion of the urinary metabolite of melatonin
Time Frame: 6 weeks after the beginning of the treatment
Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)
6 weeks after the beginning of the treatment
Severity of autistic impairments
Time Frame: 6 weeks after the beginning of the treatment
Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale
6 weeks after the beginning of the treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rennes University Hospital

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

January 25, 2013

First Submitted That Met QC Criteria

January 29, 2013

First Posted (Estimated)

January 31, 2013

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 17, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANSM A91245-56

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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