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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2010 by The Hospital for Sick Children.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT01161108
First received: July 9, 2010
Last updated: July 12, 2010
Last verified: July 2010
  Purpose

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.


Condition Intervention Phase
Epilepsy
Insomnia
Developmental Disability
Drug: Fast Release Melatonin (FR MLT)
Drug: Fast Release Placebo
Drug: Timed Release Melatonin (TR MLT)
Drug: Timed Release Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial Pilot Project to Evaluate the Efficacy of Melatonin in Children With Insomnia, Intractable Epilepsy and Neurodevelopmental Disabilities

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Change in duration of nocturnal sleep time [ Time Frame: Baseline, Weeks 9 and 13 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline, Weeks 9 and 13 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline, Weeks 9 and 13 ] [ Designated as safety issue: No ]

    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



Estimated Enrollment: 30
Study Start Date: July 2010
Estimated Study Completion Date: September 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).

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.
Other Name: Sleep Tight TM by Nature's Harmony® Melatonin
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.

Active Comparator: 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).

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.

Other Name: Melatonin Timed Release by General Nutrition Canada
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.


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.

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01161108

Contacts
Contact: Shelly Weiss, MD 416-813-6332 shelly.weiss@sickkids.ca

Locations
Canada, Ontario
The Hospital for Sick Children Not yet recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Shelly Weiss, MD    416 813 6332    shelly.weiss@sickkids.ca   
Principal Investigator: Shelly Weiss, MD         
Sub-Investigator: Robyn Stremler, PhD         
Sub-Investigator: Maria Zak         
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Shelly Weiss, MD The Hospital for Sick Children, Toronto Canada
  More Information

No publications provided

Responsible Party: Shelly Weiss/ Principal Investigator, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT01161108     History of Changes
Other Study ID Numbers: 1000010842
Study First Received: July 9, 2010
Last Updated: July 12, 2010
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
Pediatrics
Epilepsy
Insomnia
Melatonin

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Developmental Disabilities
Epilepsy
Mental Disorders Diagnosed in Childhood
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Melatonin
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on July 22, 2014