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

Controlled-Release Melatonin (Melatonin CR)for the Treatment of Impaired Sleep Maintenance (ISM) in 4-8 Year Old Children With Autism Spectrum Disorders (ASD).

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.

Study Overview

• Status: Terminated
• Conditions: Sleep Disorder
• Intervention / Treatment: Drug: Natrol

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-5380
      • University of Nebraska Medical Center-Munroe Meyer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 6 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression-Improvement	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.	2 weeks

Collaborators and Investigators

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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: December 14, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimated): December 16, 2009

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Autism Spectrum Disorders; Impaired sleep maintenance
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Sleep Wake Disorders; Autism Spectrum Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 0401-09-FB