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

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.

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.