Trial of Melatonin to Improve Sleep in Children With Epilepsy and Neurodevelopmental Disabilities

Epilepsy Clinical Trial

Official title:

A Randomized Controlled Trial Pilot Project to Evaluate the Efficacy of Melatonin in Children With Insomnia, Intractable Epilepsy and Neurodevelopmental Disabilities

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01161108
• Other study ID #: 1000010842
• Status: Completed
• Phase: Phase 3
• First received: July 9, 2010
• Last updated: December 1, 2014
• Start date: July 2010
• Est. completion date: June 2012

Study information

• Verified date: December 2014
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to evaluate the safety and efficacy of oral melatonin in improving sleep continuity in children with epilepsy and neurodevelopmental delay who have chronic insomnia by comparing Fast Release Melatonin (FR MLT) to placebo and Timed Release Melatonin (TR MLT) with placebo in a randomized cross-over design trial.

Description:

Sleep disturbance in children is a universal concern. The prevalence of sleep disorders may be as high as 80% in children with neurodevelopmental disabilities. The majority of the parental complaints are with difficulty getting children to settle to sleep at night and stay asleep (insomnia).

Two recent studies comparing children with epilepsy to matched controls or to sibling controls both concluded that children with epilepsy have more daytime sleepiness that may be due to underlying sleep disorders, and significantly greater sleep problems than their non-epileptic peers.

Endogenous melatonin is thought to synchronize the sleep-wake pattern with the light-dark cycle of the normal day. Exogenous melatonin has been found to be effective in reducing sleep onset latency, increasing sleep duration, and increasing sleep efficiency in a meta-analysis of subjects with sleep disorders. The melatonin in fast release preparations is released quickly and has a short half-life of less than 1 hour. It is most helpful in decreasing sleep onset latency (the time to fall asleep). The melatonin in timed release tablets is released in a slower more sustained way and, in a small study in children with severe neurodevelopmental disabilities, was more useful for sleep maintenance.

Fast release melatonin has been shown to be effective in a study of children with multiple disabilities and in one trial in children with epilepsy. Further rigorous evaluation of melatonin is needed as the validity of these studies is limited by their lack of blinding, small sample sizes, and subjective methods of sleep-wake outcome evaluations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: June 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 17 Years

Eligibility

Inclusion Criteria:

• Children aged 5-17 years

• Children with epilepsy with at least 2 partial or generalized seizures per month over the last 3 months prior to starting the trial

• Children with neurodevelopmental disability, i.e. significant delay in development requiring special educational setting or educational assistant

• Anti-epileptic drugs (AED's) expected to remain unchanged for duration of trial (14 weeks)

• Not currently using melatonin or any other medication for sleep Subjects will be eligible if they have previous use of melatonin as long as there is a washout period of at least 1 week. Similarly, children taking natural health products for sleep will be included as long as there is a 30 day washout period prior to study enrollment.

• Chronic insomnia - reported by parent(s) to include one of the following: sleep onset latency of greater than one hour, duration of sleep less than 8.5 hours per night with either/or both these problems occurring at least 3 nights per week and that have occurred 3 months prior to trial, or night wakings of more than 2 per night for same time period

Exclusion Criteria:

• Planned epilepsy surgery or change in AED's during treatment trial

• Sleep disturbances that are treatable such as obstructive sleep apnea

• Allergy or severe adverse effects to melatonin

• Allergy or severe adverse effects to any of the ingredients of the study product or placebo (e.g. lactose)

• Lactose intolerance

• Pregnant

• Breastfeeding

• Known liver disease

• Ketogenic diet

• Other drugs being used for sedation

• Immunosuppressive drugs

• Known blood clotting abnormalities or who are on anticoagulant therapy (e.g. warfarin, blood thinners)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Developmental Disabilities
• Developmental Disability
• Epilepsy
• Insomnia

Intervention

Drug:
• Fast Release Melatonin (FR MLT)
3mg capsules of melatonin will be used. The dose of FR MLT will be 3 mg for children less than or equal to 20 kg, and 6 mg for children greater than 20 kg. The study medication will be given one hour before bedtime, once daily.
• Fast Release Placebo
A matching FR MLT placebo will be compounded by the SickKids research pharmacy. The dose of Fast Release Placebo will be 3 mg for children less than or equal to 20 kg, and 6 mg for children greater than 20 kg. The study medication will be given one hour before bedtime, once daily.
• Timed Release Melatonin (TR MLT)
3 mg capsules will be used. The dose of TR MLT will be will be 3 mg for children less than or equal to 20 kg, and 6 mg for children greater than 20 kg. The study medication will be given one hour before bedtime, once daily.
• Timed Release Placebo
A matching TR MLT placebo will be compounded by the SickKids research pharmacy. The dose of Timed Release Placebo will be will be 3 mg for children less than or equal to 20 kg, and 6 mg for children greater than 20 kg. The study medication will be given one hour before bedtime, once daily.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in duration of nocturnal sleep time	We will measure the sleep time between 7 pm and 9 am.; The measures will be analyzed to determine the change from baseline and change between active treatment and placebo.	Baseline, Weeks 9 and 13	No
Secondary	Sleep onset latency	We will measure the interval of time between lights out and the onset of sleep.; The measures will be analyzed to determine the change from baseline and change between active treatment and placebo.	Baseline, Weeks 9 and 13	No
Secondary	Sleep efficiency	We will measure the time sleeping/time in bed between lights out at night and lights on in the morning.; The measures will be analyzed to determine the change from baseline and change between active treatment and placebo	Baseline, Weeks 9 and 13	No