Melatonin Dose-effect Relation in Childhood Autism (MELADOSE)

Rennes University Hospital

Status and phase: Completed; Phase 2

Conditions: Childhood Autism

Treatments: Drug: melatonin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01780883

ANSM A91245-56

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: Male

Ages: 6 to 8 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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34 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

2 mg melatonin

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: melatonin

4 mg melatonin

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: melatonin

10 mg melatonin

Experimental group

Description:

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

Treatment:

Drug: melatonin