Childhood AutismPhase 2MELADOSENCT01780883
Melatonin Dose-effect Relation in Childhood Autism
A Phase 2 study testing melatonin in people with Childhood Autism, run by Rennes University Hospital at 4 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 8 years, men only
- Conditions the study is for
- Childhood Autism
- What is being tested?
- melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 4 sitesFrance
- Study dates
- Feb 2013to Sep 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 8 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
4 sites in 1 country.
France4 sites
Service de Psychiatrie de l'Enfant et de l'Adolescent - Hôpital de la Pitié-Salpêtrière
Paris, 75013
Centre Hospitalier Spécialisé Henri Laborit
Poitiers, 86280
Service de Psychothérapie de l'Enfant et de l'Adolescent - Hôpital Robert Debré
Reims, 51092
Pôle de Psychiatrie de l'Enfant et de l'Adolescent - Centre Hospitalier Guillaume Régnier
Rennes, 35200
About this study
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.
Read the 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
- Being tested
- melatonin, Placebo
- Keywords
- melatonin, childhood autism, 6-Sulphatoxymelatonin, autistic disorder, dose-effect relation
- Medical subject headings
- Autistic Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
melatoninDrug
Also called Circadin®
PlaceboDrug
Placebo tablets of Circadin®
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 5 tablets of placebo once a day, an hour before falling asleep, for 6 weeks. Receives: 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. Receives: 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. Receives: Drug: melatonin; Drug: Placebo |
| 10 mg melatonin | Experimental | 5 tablets of 2mg melatonin once a day, an hour before falling asleep, for 6 weeks. Receives: Drug: melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of autistic disorder
Measured: 6 weeks after the beginning of the treatment.
Secondary outcomes (8)
Severity of autistic impairments
Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ADOS (Autism Diagnostic Observation Scale)
Measured: 3 weeks after the beginning of the treatment
Sleep problems
Sleep problems will be assessed using a parental questionnaire and an actimetry sensor in the child recording
Measured: 3 weeks after the beginning of the treatment
Excretion of the urinary metabolite of melatonin
Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)
Measured: 3 weeks after the beginning of the treatment
Severity of autistic impairments
Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale
Measured: 3 weeks after the beginning of the treatment
Severity of autistic impairments
Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ADOS (Autism Diagnostic Observation Scale)
Measured: 6 weeks after the beginning of the treatment
Sleep problems
Sleep problems will be assessed using a parental questionnaire and an actimetry sensor in the child recording
Measured: 6 weeks after the beginning of the treatment
Excretion of the urinary metabolite of melatonin
Diurnal and nocturnal excretion of the urinary metabolite of melatonin (6-Sulphatoxymelatonin)
Measured: 6 weeks after the beginning of the treatment
Severity of autistic impairments
Severity of autistic impairments (global severity of autistic disorder and anxiety) using the ICG scale
Measured: 6 weeks after the beginning of the treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionJul 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Childhood AutismStudies of the same condition, open and under way.
- More trials run by Rennes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rennes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Guillaume Régnier, RENNES
- Responsible party
- Sponsor
- Investigators
- Sylvie TORDJMAN, MD, PhD, Principal investigator, Centre Hospitalier Guillaume Régnier, RENNESEric BELLISSANT, MD, PhD, Study chair, Rennes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01780883
- Sponsor's protocol ID
- ANSM A91245-56
- Acronym
- MELADOSE
- Status last verified
- Jan 2025
- First submitted
- 25 Jan 2013
- Last updated
- 20 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 28503116
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin Dose-effect Relation in Childhood Autism
- ClinicalTrials.gov ID
- NCT01780883
- Acronym / sponsor ID
- MELADOSE / ANSM A91245-56
- Conditions
- Childhood Autism
- Keywords
- melatonin, childhood autism, 6-Sulphatoxymelatonin, autistic disorder, dose-effect relation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Rennes University HospitalUniversity, hospital or other
- Collaborators
- Centre Hospitalier Guillaume Régnier, RENNES
- Study start
- Feb 2013
- Primary completion
- Jul 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 31 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo5 tablets of placebo once a day, an hour before falling asleep, for 6 weeks. |
| 2 mg melatonin | Experimental | Drug: melatonin, Drug: Placebo1 tablet of 2mg melatonin and 4 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks. |
| 4 mg melatonin | Experimental | Drug: melatonin, Drug: Placebo2 tablets of 2mg melatonin and 3 tablets of its placebo once a day, an hour before falling asleep, for 6 weeks. |
| 10 mg melatonin | Experimental | Drug: melatonin5 tablets of 2mg melatonin once a day, an hour before falling asleep, for 6 weeks. |
Who may qualify
- Ages
- 6 to 8 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| melatoninAlso: Circadin® | Drug | 10 mg melatonin, 2 mg melatonin, 4 mg melatonin |
| PlaceboPlacebo tablets of Circadin® | Drug | 2 mg melatonin, 4 mg melatonin, Placebo |
Primary outcome
Severity of autistic disorder
Time frame: 6 weeks after the beginning of the treatment.
8 secondary outcomes
Severity of autistic impairments
Time frame: 3 weeks after the beginning of the treatment
Sleep problems
Time frame: 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
Severity of autistic impairments
Time frame: 3 weeks after the beginning of the treatment
Severity of autistic impairments
Time frame: 6 weeks after the beginning of the treatment
Sleep problems
Time frame: 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
Severity of autistic impairments
Time frame: 6 weeks after the beginning of the treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2025.
- Results publication: PubMed 28503116Tordjman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sylvie TORDJMAN, MD, PhD principal investigator
Centre Hospitalier Guillaume Régnier, RENNES
Eric BELLISSANT, MD, PhD study chair
Rennes University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing melatonin in people with Childhood Autism, run by Rennes University Hospital at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of autistic disorder (time frame: 6 weeks after the beginning of the treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01780883, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2025.