Melatonin for Sleep in Children With Autism (NICHD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00927030
Recruitment Status : Completed
First Posted : June 24, 2009
Last Update Posted : July 2, 2012
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Beth Ann Malow, Vanderbilt University

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).

Condition or disease Intervention/treatment Phase
Autistic Disorder Insomnia Drug: supplemental liquid melatonin Drug: flavored liquid or liquid supplemental melatonin Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Care Provider)
Primary Purpose: Treatment
Official Title: Melatonin for Sleep in Children With Autism: Safety Tolerability and Dose
Study Start Date : January 2008
Actual Primary Completion Date : April 2010
Actual Study Completion Date : October 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: Pharmacokinetic
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.
Drug: supplemental liquid melatonin
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.
Other Name: Natrol brand liquid melatonin

Placebo Comparator: flavored inert liquid
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.
Drug: flavored liquid or liquid supplemental melatonin
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.
Other Name: Inert flavored liquid manufactored by PharmaCare in Mt. Juliet TN. A certificate of analysis is on file for this compounded liquid.

Primary Outcome Measures :
  1. Determine dose-response, tolerability, and adverse effects of melatonin in 30 children with autism. [ Time Frame: Two Years from study start ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]

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Ages Eligible for Study:   4 Years to 10 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00927030

United States, Tennessee
Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232-2551
Sponsors and Collaborators
Vanderbilt University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Beth A Malow, MD, MS Vanderbilt University Medical Center

Responsible Party: Beth Ann Malow, Professor, Departments of Neurology and Pediatrics, Vanderbilt University Identifier: NCT00927030     History of Changes
Other Study ID Numbers: 071269
First Posted: June 24, 2009    Key Record Dates
Last Update Posted: July 2, 2012
Last Verified: June 2012

Keywords provided by Beth Ann Malow, Vanderbilt University:

Additional relevant MeSH terms:
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Sleep Wake Disorders
Autistic Disorder
Nervous System Diseases
Mental Disorders
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants