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

NCT ID: NCT01161108

Last Updated: 2014-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2012-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Epilepsy Insomnia Developmental Disability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Group A: Fast Release Melatonin

Subjects will be randomized to one of the two treatment arms and to the order of study medication v.s. placebo.

The subject will undergo the assigned treatment for 7 weeks (3 weeks of study drug, a one week wash-out and 3 weeks of placebo, or vice versa).

Group Type ACTIVE_COMPARATOR

Fast Release Melatonin (FR MLT)

Intervention Type DRUG

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

Intervention Type DRUG

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.

Group B: Timed Release Melatonin

Subjects will be randomized to one of the two treatment arms and to the order of study medication v.s. placebo.

The subject will undergo the assigned treatment for 7 weeks (3 weeks of study drug, a one week wash-out and 3 weeks of placebo, or vice versa).

Group Type ACTIVE_COMPARATOR

Timed Release Melatonin (TR MLT)

Intervention Type DRUG

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

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Sleep Tight TM by Nature's Harmony® Melatonin Melatonin Timed Release by General Nutrition Canada

Eligibility Criteria

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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)
Minimum Eligible Age

5 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Hospital for Sick Children

OTHER

Sponsor Role lead

Responsible Party

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Shelly Weiss

Staff neurologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shelly Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto Canada

Locations

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The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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Canada

Other Identifiers

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1000010842

Identifier Type: -

Identifier Source: org_study_id