Melatonin CR for the Treatment of Impaired Sleep Maintenance in 4-8 Year Old Children With Autism Spectrum Disorders

• Sponsor: University of Nebraska (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01033565
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 10
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research is to see the effects (good and bad) of Melatonin CR on sleep in 4-8 year old children with autism spectrum disorders and sleep problems.

Condition or Disease	Intervention/Treatment	Phase
Sleep Disorder	Drug: Natrol	Phase 4

Detailed Description

The title of this acute, open-label pilot study is "Controlled Release Melatonin (Melatonin CR) for the treatment of impaired sleep maintenance (ISM) in 4-8 year old children with autism spectrum disorders (ASD)." Maintenance of sleep is a significant challenge in the treatment of children with neurodevelopmental disabilities including ASDs. Night awakening or early morning waking can have detrimental effects on these children's daytime behavior and the functioning of their household. Sleep problems in the ASD population are generally managed first with behavioral interventions and, when these are not successful, pharmacologic therapy. Most medications effect sleep onset and not sleep maintenance. This study investigates the effectiveness of Melatonin CR for managing ISM in 4-8 year old children with ASD. Twenty patients will be recruited from the Developmental/Behavioral Pediatrics Clinic at the Munroe Meyer Institute at the University of Nebraska Medical Center. Inclusion criteria are male and female children ages 4-8 years with a diagnosis of an ASD, including Pervasive Developmental Disorder NOS (PDD, NOS), Asperger's Syndrome, or Autistic Disorder, parent/guardian consent for participation, stable psychotropic medication treatment for at least 4 weeks, and a documented history of ISM based on parent-report, somnolog and Child Sleep Habits Questionnaire (CSHQ), and a clinician rating of ≥4 (moderately ill) on the Clinical Global Impression-Severity (CGI-S) Scale. Patients will be excluded if they have been treated with Melatonin or Melatonin CR in the past month, failed treatment with Melatonin CR, or if they have a previously un-evaluated medical condition which may be causing the ISM. Following the completion of a somnolog and standardized questionnaires, the patients will be treated for 10-14 days with melatonin CR. Somnologs will be completed during treatment, and standardized parent questionnaires, CGI-S, and adverse event collection will be repeated at the end of Melatonin CR therapy. Response will be defined as a Clinical Global Impression-Improvement (CGI-I) score of 1 or 2 (much or very much improved). These will be compared to baseline ratings. Following the completion of the study protocol, all patients will continue to be followed in the Developmental Pediatrics clinic. Data from this acute pilot trial can be used to evaluate the appropriateness of a larger study to determine optimal therapy for patients with ASD and ISM.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Controlled-Release Melatonin (Melatonin CR)for the Treatment of Impaired Sleep Maintenance (ISM) in 4-8 Year Old Children With Autism Spectrum Disorders (ASD).
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Natrol Subjects receive Natrol (sustained release melatonin) 5mg tablet 30 minutes prior to bedtime for 10 to 14 days	Drug: Natrol; 5mg of sustained released melatonin. One tablet given 30 minutes prior to bedtime.; Other Names: Sustained release melatonin

Outcome Measures

Primary Outcome Measures

1. Clinical Global Impression-Improvement [2 weeks]

   Assigns numerical score indicating level of improvement compared to baseline. Scale is rated from 1-7: 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; 7= very much worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 8 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female children,

• ages 4-8 years,

• diagnosed with an ASD, including

• Pervasive Developmental Disorder NOS (PDD, NOS),

• Asperger's Syndrome, or

• Autistic Disorder, and followed in the Munroe Meyer Developmental Pediatrics Clinic. Documented impaired sleep maintenance (ISM) based on parent-report and 7 day somnolog (sleep diary).

• Clinician rating of 4 (moderately ill) or worse on CGI-S. Rating is based on the clinician's experience with evaluating and treating this patient population.

• Previous discussion during a clinic appointment about sleep difficulties, including review of sleep hygiene and basic behavioral interventions/strategies.

• Current problems of overnight awakenings recorded on the Children's Sleep Habits Questionnaire (CSHQ) despite behavioral intervention.

• Stable psychotropic medication treatment for the past 4 weeks.

Exclusion Criteria:

Treatment with Melatonin or Melatonin CR during the past month or previous failed treatment with Melatonin CR.

Presence of a previously unevaluated medical condition which may be the etiology of the nighttime awakenings. There is no contraindication for use of Melatonin CR in patients with obstructive sleep apnea.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Nebraska Medical Center Munroe Meyer Institute	Omaha	Nebraska	United States	68198-5380

Sponsors and Collaborators

• University of Nebraska

Investigators

• Principal Investigator: Howard Needelman, MD, University of Nebraska

Study Documents (Full-Text)

None provided.

More Information

Publications

• Braam W, Smits MG, Didden R, Korzilius H, Van Geijlswijk IM, Curfs LM. Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol. 2009 May;51(5):340-9. doi: 10.1111/j.1469-8749.2008.03244.x.

• Responsible Party: Howard Needelman, MD, Associate Professor, Pediatrics, University of Nebraska
• ClinicalTrials.gov Identifier: NCT01033565
• Other Study ID Numbers: 401-09
• First Posted: Dec 16, 2009
• Last Update Posted: Sep 9, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Howard Needelman, MD, Associate Professor, Pediatrics, University of Nebraska: Impaired sleep maintenance; Autism Spectrum Disorders; Pediatric
• Additional relevant MeSH terms: Sleep Wake Disorders; Disease; Autism Spectrum Disorder; Melatonin

Study Results

Participant Flow

Recruitment Details	Only one subject was recruited who met criteria to participate.
Pre-assignment Detail	One subject enrolled and finished participation.

Arm/Group Title	Natrol
Arm/Group Description	Subjects receive Natrol (sustained release melatonin) 5mg tablet 30 minutes prior to bedtime for 10 to 14 days Natrol : 5mg of sustained released melatonin. One tablet given 30 minutes prior to bedtime.
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Natrol
Arm/Group Description	Subjects receive Natrol (sustained release melatonin) 5mg tablet 30 minutes prior to bedtime for 10 to 14 days Natrol : 5mg of sustained released melatonin. One tablet given 30 minutes prior to bedtime.
Overall Participants	1
Age (Count of Participants)
<=18 years	1 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Global Impression-Improvement
Description	Assigns numerical score indicating level of improvement compared to baseline. Scale is rated from 1-7: 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; 7= very much worse.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Natrol
Arm/Group Description	Subjects receive Natrol (sustained release melatonin) 5mg tablet 30 minutes prior to bedtime for 10 to 14 days Natrol : 5mg of sustained released melatonin. One tablet given 30 minutes prior to bedtime.
Measure Participants	1
Number [units on a scale]	2

Adverse Events

Arm/Group Title	Natrol
Arm/Group Description	Subjects receive Natrol (sustained release melatonin) 5mg tablet 30 minutes prior to bedtime for 10 to 14 days Natrol : 5mg of sustained released melatonin. One tablet given 30 minutes prior to bedtime.
All Cause Mortality
	Natrol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Natrol
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Natrol
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

Unable to recruit a sufficient number of subjects to complete the study as designed.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.