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Melatonin for Sleep in Children With Autism (NICHD)

Primary Purpose

Autistic Disorder, Insomnia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
supplemental liquid melatonin
flavored liquid or liquid supplemental melatonin
Sponsored by
Vanderbilt University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autistic Disorder focused on measuring Autism, children, sleep, insomnia

Eligibility Criteria

4 Years - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Children with autism ages 4-10 years.
  • Diagnosis of autism based on Autism Diagnostic Observation Schedule (ADOS).
  • Time to fall asleep of 30 minutes or longer by parent report at least 3 nights/week in the last 3 months.
  • Children may take seasonal allergy medications.
  • Children may take the following medications for the same dose at least 3 months: Citalopram (Celexa), Escitalopram (Lexapro), Amphetamine-dextroamphetamine (Adderall), Atomoxetine (Strattera), Methylphenidate(Ritalin), Dextroamphetamine(Dexedrine), Risperidone (Risperdal.

Exclusion Criteria:

  • Children taking medications other than those in the inclusion criteria.
  • Children with primary sleep disorder other than insomnia (such as sleep-disordered breathing).
  • Children with non-febrile unprovoked epileptic seizure within the last two years.
  • Children with liver disease or high fat diets, as melatonin metabolism may be affected in these children.
  • Children who are visually impaired (partially or completely blind) as light suppresses melatonin synthesis and these children may have altered diurnal melatonin rhythms.
  • Children with known genetic syndromes co-morbid with autism including fragile X, Down syndrome, neurofibromatosis, or tuberous sclerosis.
  • Children who have outside normal limits on blood work for complete blood count, liver and renal function and hormone levels of ACTH, cortisol, LH, FSH, prolactin, testosterone and estradiol.
  • Tanner staging beyond level 1 at any time point in the study.
  • Children whose assessment score does not place them on the autism spectrum.

Sites / Locations

  • Vanderbilt Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pharmacokinetic

flavored inert liquid

Arm Description

We hope to target 12 of the 30 children to be enrolled for this study to participate in a pharmacokinetic arm of the study. These 12 children would be receiving overnight sleep studies prior to receiving the first dose of melatonin and again at about every 3 week intervals each time the dose increases until the child is falling asleep within 30 minutes of bedtime on 5/7 nights per week. During the sleep studies an intravenous catheter will be placed in the child's arm to sample small amounts of blood throughout the day (about 3 teaspoons of blood)to allow us to look at how melatonin is produced in children with autism who have sleep problems.

Of the 30 targeted participants, 18 will be randomized at the first three week dosing period {1mg of melatonin}. The randomization will be single blind to the parent in a 5:1 ratio (15 children will receive melatonin, and 3 children will receive a flavored placebo at the first 3-week period only). After the initial 3-week dose cycle of 1 mg, all children randomized to placebo will begin 3 mg of melatonin and will continue in dose increase (6mg, 9 mg)until they meet the criteria of falling asleep within 30 minutes of bedtime 5/7 nights per week. No child will take more than 9 mg.

Outcomes

Primary Outcome Measures

Determine dose-response, tolerability, and adverse effects of melatonin in 30 children with autism.

Secondary Outcome Measures

A sub-set of 12 children will be studied to characterize the pharmacokinetic profile of orally administered melatonin.
A group of behavioral and parental stress measures will be piloted for the participants in this study.

Full Information

First Posted
June 22, 2009
Last Updated
June 28, 2012
Sponsor
Vanderbilt University
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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1. Study Identification

Unique Protocol Identification Number
NCT00927030
Brief Title
Melatonin for Sleep in Children With Autism
Acronym
NICHD
Official Title
Melatonin for Sleep in Children With Autism: Safety Tolerability and Dose
Study Type
Interventional

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
January 2008 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if liquid supplemental melatonin is an effective treatment for children with autism who have sleep problems related to insomnia (difficulty falling asleep).
Detailed Description
Sleep difficulties in children with autism spectrum disorders (ASD) are common reasons why parents seek medical intervention for their children. Identifying a safe and effective pharmacologic agent that promotes sleep in ASD would favorably impact the lives of these children and their families. In this study we plan to determine the dose-response, tolerability and any adverse effects of supplemental melatonin in 30 children with ASD.The melatonin dose levels are 1mg, 3mg, 6mg, and 9mg. After a 3 week baseline period, the child will begin melatonin at 1mg and will dose escalate every three weeks until he/she is falling asleep within 30 minutes of bedtime at least 5/7 nights per week. No child will take more than 9 mg of supplemental melatonin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autistic Disorder, Insomnia
Keywords
Autism, children, sleep, insomnia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
Care Provider
Allocation
Randomized
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pharmacokinetic
Arm Type
Experimental
Arm Description
We hope to target 12 of the 30 children to be enrolled for this study to participate in a pharmacokinetic arm of the study. These 12 children would be receiving overnight sleep studies prior to receiving the first dose of melatonin and again at about every 3 week intervals each time the dose increases until the child is falling asleep within 30 minutes of bedtime on 5/7 nights per week. During the sleep studies an intravenous catheter will be placed in the child's arm to sample small amounts of blood throughout the day (about 3 teaspoons of blood)to allow us to look at how melatonin is produced in children with autism who have sleep problems.
Arm Title
flavored inert liquid
Arm Type
Placebo Comparator
Arm Description
Of the 30 targeted participants, 18 will be randomized at the first three week dosing period {1mg of melatonin}. The randomization will be single blind to the parent in a 5:1 ratio (15 children will receive melatonin, and 3 children will receive a flavored placebo at the first 3-week period only). After the initial 3-week dose cycle of 1 mg, all children randomized to placebo will begin 3 mg of melatonin and will continue in dose increase (6mg, 9 mg)until they meet the criteria of falling asleep within 30 minutes of bedtime 5/7 nights per week. No child will take more than 9 mg.
Intervention Type
Drug
Intervention Name(s)
supplemental liquid melatonin
Other Intervention Name(s)
Natrol brand liquid melatonin
Intervention Description
Liquid melatonin will be given to the parent. There are 4 dose levels (1mg, 3mg, 6 mg, and 9mg)of melatonin that will be used at 3 week intervals. The child will start with 1mg and the dose will be increased at 3 week intervals until the child is falling asleep within 30 minutes of bedtime on 5/7 nights per week. Once this goal is reached the child will stay on that dose through the remainder of the study.
Intervention Type
Drug
Intervention Name(s)
flavored liquid or liquid supplemental melatonin
Other Intervention Name(s)
Inert flavored liquid manufactored by PharmaCare in Mt. Juliet TN. A certificate of analysis is on file for this compounded liquid.
Intervention Description
Single blind for parents at initial 3-weeks dose period of 1 mg melatonin for 18 children where 3/18 children will receive placebo and 15/18 children will receive melatonin study drug. Each bottle will be labeled as: Flavored liquid placebo/or liquid melatonin. After this initial 3-week period all children will receive known melatonin in bottles that state this.
Primary Outcome Measure Information:
Title
Determine dose-response, tolerability, and adverse effects of melatonin in 30 children with autism.
Time Frame
Two Years from study start
Secondary Outcome Measure Information:
Title
A sub-set of 12 children will be studied to characterize the pharmacokinetic profile of orally administered melatonin.
Time Frame
2 years from start of study
Title
A group of behavioral and parental stress measures will be piloted for the participants in this study.
Time Frame
2 years from start of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children with autism ages 4-10 years. Diagnosis of autism based on Autism Diagnostic Observation Schedule (ADOS). Time to fall asleep of 30 minutes or longer by parent report at least 3 nights/week in the last 3 months. Children may take seasonal allergy medications. Children may take the following medications for the same dose at least 3 months: Citalopram (Celexa), Escitalopram (Lexapro), Amphetamine-dextroamphetamine (Adderall), Atomoxetine (Strattera), Methylphenidate(Ritalin), Dextroamphetamine(Dexedrine), Risperidone (Risperdal. Exclusion Criteria: Children taking medications other than those in the inclusion criteria. Children with primary sleep disorder other than insomnia (such as sleep-disordered breathing). Children with non-febrile unprovoked epileptic seizure within the last two years. Children with liver disease or high fat diets, as melatonin metabolism may be affected in these children. Children who are visually impaired (partially or completely blind) as light suppresses melatonin synthesis and these children may have altered diurnal melatonin rhythms. Children with known genetic syndromes co-morbid with autism including fragile X, Down syndrome, neurofibromatosis, or tuberous sclerosis. Children who have outside normal limits on blood work for complete blood count, liver and renal function and hormone levels of ACTH, cortisol, LH, FSH, prolactin, testosterone and estradiol. Tanner staging beyond level 1 at any time point in the study. Children whose assessment score does not place them on the autism spectrum.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beth A Malow, MD, MS
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2551
Country
United States

12. IPD Sharing Statement

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Melatonin for Sleep in Children With Autism

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