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

Primary Purpose

Epilepsy, Insomnia, Developmental Disability

Status

Completed

Phase

Phase 3

Locations

Canada

Study Type

Interventional

Intervention

Fast Release Melatonin (FR MLT)

Fast Release Placebo

Timed Release Melatonin (TR MLT)

Timed Release Placebo

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Pediatrics, Epilepsy, Insomnia, Melatonin

Eligibility Criteria

5 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Group A: Fast Release Melatonin

Group B: Timed Release Melatonin

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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

Full Information

NCT ID

NCT01161108

First Posted

July 9, 2010

Last Updated

December 1, 2014

Sponsor

The Hospital for Sick Children

1. Study Identification

Unique Protocol Identification Number

NCT01161108

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Completed

Study Start Date

July 2010 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Hospital for Sick Children

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy, Insomnia, Developmental Disability

Keywords

Pediatrics, Epilepsy, Insomnia, Melatonin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Crossover Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group A: Fast Release Melatonin

Arm Type

Active Comparator

Arm Description

Arm Title

Group B: Timed Release Melatonin

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Fast Release Melatonin (FR MLT)

Other Intervention Name(s)

Sleep Tight TM by Nature's Harmony® Melatonin

Intervention Description

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

Intervention Name(s)

Fast Release Placebo

Intervention Description

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

Intervention Name(s)

Timed Release Melatonin (TR MLT)

Other Intervention Name(s)

Melatonin Timed Release by General Nutrition Canada

Intervention Description

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

Intervention Name(s)

Timed Release Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in duration of nocturnal sleep time

Description

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.

Time Frame

Baseline, Weeks 9 and 13

Secondary Outcome Measure Information:

Title

Sleep onset latency

Description

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.

Time Frame

Baseline, Weeks 9 and 13

Title

Sleep efficiency

Description

Time Frame

Baseline, Weeks 9 and 13

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shelly Weiss, MD

Organizational Affiliation

The Hospital for Sick Children, Toronto Canada

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

12. IPD Sharing Statement

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

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