Melatonin Dose-effect Relation in Childhood Autism

NCT01780883 | Completed Phase 2 DMC

• 1 other identifier: ANSM A91245-56
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

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.

Conditions

Childhood Autism

Keywords

melatonin; childhood autism; 6-Sulphatoxymelatonin; autistic disorder; dose-effect relation

Outcome Measures

Primary Outcomes (1)

• Severity of autistic disorder

  6 weeks after the beginning of the treatment.

Secondary Outcomes (8)

• Severity of autistic impairments

  3 weeks after the beginning of the treatment

• Sleep problems

  3 weeks after the beginning of the treatment

• Excretion of the urinary metabolite of melatonin

  3 weeks after the beginning of the treatment

• Severity of autistic impairments

  3 weeks after the beginning of the treatment

• Severity of autistic impairments

  6 weeks after the beginning of the treatment

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

2 mg melatonin

EXPERIMENTAL

1 tablet of 2mg melatonin and 4 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.

Drug: melatonin; Drug: Placebo

4 mg melatonin

EXPERIMENTAL

2 tablets of 2mg melatonin and 3 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks.

Drug: melatonin; Drug: Placebo

10 mg melatonin

EXPERIMENTAL

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

Drug: melatonin

Interventions

melatonin DRUG

Also known as: Circadin®

10 mg melatonin; 2 mg melatonin; 4 mg melatonin

Placebo DRUG

Placebo tablets of Circadin®

2 mg melatonin; 4 mg melatonin; Placebo

Eligibility Criteria

• Age: 6 Years - 8 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

Sponsors & Collaborators

• Rennes University Hospital: lead
• Centre Hospitalier Guillaume Régnier, RENNES: collaborator

Study Sites (4)

Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière

Paris, 75013, France

Location

Centre Hospitalier Spécialisé Henri Laborit

Poitiers, 86280, France

Location

Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré

Reims, 51092, France

Location

Pôle de Psychiatrie de l'Enfant et de l'Adolescent - Centre Hospitalier Guillaume Régnier

Rennes, 35200, France

Location

Related 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.

  PMID: 28503116 RESULT

MeSH Terms

Conditions

Autistic Disorder

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Sylvie TORDJMAN, MD, PhD

  Centre Hospitalier Guillaume Régnier, RENNES

  PRINCIPAL INVESTIGATOR

• Eric BELLISSANT, MD, PhD

  Rennes University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 31, 2013
• Study Start: February 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 20, 2025

Record last verified: 2025-01

Locations

FR (4)