MELatonin for children with idiopathic chronic sleep onset insomnia, with or without attention deficit hyperkinesia disorder - a DOSe finding trial: a randomised placebo-controlled double-blind parallel group trial

ISRCTN	ISRCTN20033346
DOI	https://doi.org/10.1186/ISRCTN20033346
Protocol serial number	MELDOS VERSION 2.0
Sponsor	Hospital Pharmacy of the Valley of Gelderland (Ziekenhuisapotheek Gelderse Vallei) (The Netherlands)
Funder	Pharma Nord Denmark (The Netherlands)

Submission date: 13/04/2007
Registration date: 13/04/2007
Last edited: 08/11/2010

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Mental and Behavioural Disorders

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr I M van Geijlswijk
Scientific

University Medical Center Utrecht (UMCU)
Pharmacy of Faculty Animal Medicine
Ede
6716 RP
Netherlands

Phone	+31 (0)30 253 2066
Email	i.m.vangeijlswijk@vet.uu.nl

Study information

Primary study design	Interventional
Study design	Randomised, placebo controlled, parallel group, double blinded trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	MELDOS
Study objectives	Chronic sleep disorders are associated with dysfunctioning during the day. Circadian rhythm disorders are a frequently occurring cause of chronic sleep disorders. The time at which the endogenous melatonin production starts to rise plays a key-role in the synchronisation of circadian rhythms. In adults with sleep-wake rhythm disorders and late melatonin onset, exogenous melatonin, when administered at an appropriate time advances both endogenous melatonin onset and sleep-wake rhythm. Pharmacokinetics and side effects of melatonin in children might differ from those in adults. Consequently it is necessary to study the effects of melatonin not only in adults but also in children.
Ethics approval(s)	Approval received from the Medical Ethical Committee of the Utrecht University Hospital (Medisch Ethische Toetsingscommissie van het UMC Utrecht) on the 17th June 2003 (ref: 03/007).
Health condition(s) or problem(s) studied	Insomnia, Attention Deficit Hyperactivity Disorder (ADHD), sleep disorders
Intervention	The study lasts two weeks. One baseline week, followed by one treatment week with melatonin (commercially available Over The Counter [OTC] product) 0.05 mg/kg, 0.1 mg/kg, 0.15 mg/kg or placebo treatment.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Melatonin
Primary outcome measure(s)	1. Actigraphic sleep onset and offset and melatonin onset (defined as the time at which 4 pg/ml melatonin in saliva is reached) 2. Diary lights-off time 3. Sleep latency (latency between lights-off and sleep onset) 4. Sleep onset 5. Sleep duration 6. Sleep-offset and wake up time 7. Behaviour 8. Health status Actigraphy data (for measurement of primary outcomes 1, 3, 4, 5 and 6) are collected during five days of week one, and five days of week two. Saliva collection (for the measurement of primary outcome 1) is done on day seven of week one and day seven of week two, for measurement of melatonin onset. The diary is recorded during all 14 days of the trial duration (for measurements of primary outcomes 2, 7, 8, and secondary outcome). At this moment an interim analysis of the actigraphy results of week one (no medication) versus week two (with double blind placebo controlled medication) is ongoing, after 75 patients enrolled.
Key secondary outcome measure(s)	Possible side effects and adverse events will be evaluated.
Completion date	01/05/2007

Eligibility

Participant type(s)	Patient
Age group	Child
Sex	All
Target sample size at registration	150
Key inclusion criteria	1. At inclusion physical examination, medial history and inclusion/exclusion assessments will be performed. The results of a hypnogram, performed within the past two months, showing a normal sleep architecture has to be known at inclusion 2. The children and their parents have to be motivated to comply the study protocol
Key exclusion criteria	1. Child-psychiatric or family problems who can explain the sleep onset insomnia 2. Disturbed sleep architecture (hypnogram) 3. Use of Monoamine Oxidase (MAO) inhibitors 4. Children with known disturbed hepatic or renal function 5. Patients with the Roter syndrome 6. Patients with the Dubin-Johnson syndrome 7. Factors or diseases which can, according to the investigator, inhibit participation to the study 8. Medical, environmental, psychiatric or other factors, which can cause sleep onset insomnia during the trial 9. Participation in a study on the efficacy of drugs in the month preceding the inclusion 10. Mental retardation (Intelligence Quotient [IQ] less than 80) 11. Any prior use of melatonin 12. Use of hypnotics, antidepressants or neuroleptics 13. Chronic pain 14. Severe neurological or psychiatric disorder
Date of first enrolment	01/05/2004
Date of final enrolment	01/05/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

University Medical Center Utrecht (UMCU)

Ede
6716 RP
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2010		Yes	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes