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Melatonin Dose-effect Relation in Childhood Autism (MELADOSE)

This study has been completed.
Sponsor:
Collaborator:
Centre Hospitalier Guillaume Régnier, RENNES
Information provided by (Responsible Party):
Rennes University Hospital
ClinicalTrials.gov Identifier:
NCT01780883
First received: January 25, 2013
Last updated: September 4, 2013
Last verified: September 2013
  Purpose

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 Intervention Phase
Childhood Autism
Drug: melatonin
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Melatonin Dose-effect Relation in Childhood Autism

Resource links provided by NLM:


Further study details as provided by Rennes University Hospital:

Primary Outcome Measures:
  • Severity of autistic disorder [ Time Frame: 6 weeks after the beginning of the treatment. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Severity of autistic impairments [ Time Frame: 3 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ADOS (Autism Diagnostic Observation Scale)

  • Sleep problems [ Time Frame: 3 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Sleep problems will be assessed using a parental questionnaire and an actimetry sensor in the child recording

  • Excretion of the urinary metabolite of melatonin [ Time Frame: 3 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)

  • Severity of autistic impairments [ Time Frame: 3 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale

  • Severity of autistic impairments [ Time Frame: 6 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ADOS (Autism Diagnostic Observation Scale)

  • Sleep problems [ Time Frame: 6 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Sleep problems will be assessed using a parental questionnaire and an actimetry sensor in the child recording

  • Excretion of the urinary metabolite of melatonin [ Time Frame: 6 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)

  • Severity of autistic impairments [ Time Frame: 6 weeks after the beginning of the treatment ] [ Designated as safety issue: No ]
    Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale


Enrollment: 34
Study Start Date: February 2013
Study Completion Date: September 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Circadin®

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

Ages Eligible for Study:   6 Years to 8 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01780883

Locations
France
Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière
Paris, France, 75013
Centre Hospitalier Spécialisé Henri Laborit
Poitiers, France, 86280
Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré
Reims, France, 51092
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
  More Information

No publications provided

Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT01780883     History of Changes
Other Study ID Numbers: ANSM A91245-56
Study First Received: January 25, 2013
Last Updated: September 4, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Rennes University Hospital:
melatonin
childhood autism
6-Sulphatoxymelatonin
autistic disorder
dose-effect relation

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Mental Disorders
Mental Disorders Diagnosed in Childhood
Melatonin
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014