Iron Treatment of Sleep Disorders in Children With Autism Spectrum Disorder

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Autism Treatment Network
Massachusetts General Hospital
The EMMES Corporation
Health Resources and Services Administration (HRSA)
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01745497
First received: November 13, 2012
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

Autism Spectrum Disorders (ASD) are characterized by difficulties in language, social communication, and repetitive and restricted behaviors. ASD affects as many as 1 in 90-150 children. Sleep issues/insomnia is very common in children with ASD (50-80%). Insomnia has a negative impact on both the developmental and behavioral function of the child and the quality of life for the family. Causes of insomnia in children with ASD are multifactorial and can be difficult to treat effectively. Low iron stores, as manifest by low serum ferritin levels, is also common in children with ASD. Both insomnia and low iron stores are associated with Restless Legs Syndrome (RLS) and Periodic Limb Movement of Sleep (PLMS). Children with ASD often have difficulty communicating symptoms or tolerating Polysomnography (Sleep Study). This makes establishing a diagnosis of RLS or PLMS very difficult in children with ASD.


Condition Intervention Phase
Autism Spectrum Disorder
Insomnia
Drug: Ferrous sulfate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Iron Treatment of Sleep Disorders in Children With Autism Spectrum Disorder

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Improvement in sleep onset [ Time Frame: 3 month ] [ Designated as safety issue: No ]
    Improvement in sleep onset latency will be measured using actigraphy before and after treatment with iron vs placebo.


Secondary Outcome Measures:
  • Day time behavior [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Daytime behavior will be assessed using parent questionnaires. Improvement in daytime behaviors such as attention will be assessed.

  • Improvements in sleep maintenance insomnia [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Improvement in sleep maintenance insomnia will be measured using actigraphy before and after treatment with iron vs placebo.


Estimated Enrollment: 200
Study Start Date: December 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ferrous Sulfate
3mg/kg divided twice per day, 30 minutes before a meal or 2 hours after a meal
Drug: Ferrous sulfate
3mg/kg liquid
Other Name: Fer-in-Sol
Placebo Comparator: Placebo
Equivalent volume of liquid placebo administered twice daily, before a meal or 2 hours after a meal
Drug: Placebo
Equivalent volume of liquid with similar color and taste.

Detailed Description:

Autism Spectrum Disorders (ASD) are characterized by difficulties in language, social communication, and repetitive and restricted behaviors. ASD affects as many as 1 in 90-150 children. Sleep issues/insomnia is very common in children with ASD (50-80%). Insomnia has a negative impact on both the developmental and behavioral function of the child and the quality of life for the family. Causes of insomnia in children with ASD are multifactorial and can be difficult to treat effectively. Low iron stores, as manifest by low serum ferritin levels, is also common in children with ASD. Both insomnia and low iron stores are associated with Restless Legs Syndrome (RLS) and Periodic Limb Movement of Sleep (PLMS). Children with ASD often have difficulty communicating symptoms or tolerating Polysomnography (Sleep Study). This makes establishing a diagnosis of RLS or PLMS very difficult in children with ASD. Because polysomnography is not well tolerated in children with ASD and cannot measure sleep over time in a natural environment, improvements in sleep with treatment with iron will be measured by standard actigraphy (a watch that measures movements during sleep) and sleep diaries. The investigators also propose to evaluate periodic limb movement index (PLMI) as a predictor of response to iron treatment for insomnia in children with ASD, as measured by the PAM-RL, an actigraph designed to measure PLMS. The investigators will collect secondary data regarding attention and behavior over the course of the study to monitor improvement in daytime functioning in both groups. Many clinicians will empirically treat children with ASD, insomnia and low ferritin levels (< 50ng/ml) with iron. This is based on data from a previous open label trial demonstrating subjective improvement in restless sleep in children with ASD with low/low normal ferritin levels who were treated with iron. In order to evaluate the efficacy of such treatment, The investigators propose a randomized placebo-controlled trial of oral elemental iron for treatment of insomnia in children with ASD and ferritin levels that are low but above the laboratory cut off for deficiency. This study will evaluate the effectiveness of treatment of insomnia with oral ferrous sulfate (iron) at a dose of 3mg/kg divided twice per day for 3 months compared to placebo.

  Eligibility

Ages Eligible for Study:   2 Years to 10 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Child has a clinical diagnosis of autism spectrum disorder, meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria, confirmed by the Autism Diagnostic Observation Schedule.
  • Age 2 years to 10 years 11 months.
  • Child has sleep onset latency of greater than 40 minutes on 3 or more nights per week, an average greater than 30 minutes per night, or night waking at least 3 times per week requiring parental intervention or lasting >20 minutes per night.
  • A mean sleep latency of 30 minutes or more, or night waking will be need to be confirmed by 7 days of scorable actigraphy data prior to randomization.
  • Ferritin between 17ng/ml and 49 ng/ml, confirmed at a central lab.
  • The child has been screened for medical conditions that affect sleep by their clinician and referred for subspecialty evaluation, as needed, for coexisting disorders (e.g., Gastrointestinal reflux disease, epilepsy).
  • We will include children with coexisting medical, psychiatric, and neurological disorders as long as they have been evaluated by a physician and a treatment plan has been implemented, with the child on a stable dose of medication for one month
  • Parents and their child are willing and able to provide informed consent (and assent, depending on child's age and cognitive function) and to cooperate with study procedures. Children with coexisting intellectual disability who can cooperate with study procedures are eligible.
  • A child with known genetic syndromes comorbid with autism spectrum disorder (ASD), including Fragile X, down syndrome, neurofibromatosis, or tuberous sclerosis will be included as long as they meet other eligibility criteria.

Exclusion Criteria:

  • Family history of hemochromatosis
  • Elevated C-reactive protein (CRP) (may be repeated and enrolled once inflammation has resolved)
  • Anemia - low hemoglobin (<11.0 g/dL for children <5 and <12.0 g/dL for children 6-11) (unless cause of anemia is known, is not due to iron deficiency, and there would be no contraindication to treatment with iron.)
  • Fever in past week or active infection.
  • Current treatment with iron in any amount other than that in a multivitamin
  • Severe constipation/GI issues that are not adequately managed
  • Treatable sleep and medical condition such as obstructive sleep apnea or severe eczema that are not adequately managed.
  • A child who is currently participating in other interventional research studies.
  • Child with a seizure in the previous 2 years.
  • A child taking medications that significantly influence RLS symptoms such as antinausea drugs (prochlorperazine, promethazine, triethylpyrazine or metoclopramide), antipsychotic drugs (haloperidol or phenothiazine derivatives such as chlorpromazine, promazine, triflupromazine, methotrimeprazine, fluphenazine, mesoridazine, perphenazine, thioridazine, and trifluoperazine), antidepressants that increase serotonin only if the onset of sleep issues was associated with starting the medication, and some cold and allergy medications-that contain sedating antihistamines(methdilazine, promethazine, trimeprazine).
  • A child taking a medication that has a significant drug interaction with iron that cannot be addressed by the timing of administration such as Cholestyramine and Colestipol, Tagamet, Zantac, Pepcid, Axid, ACE inhibitors (captopril, enalapril, and lisinopril), carbidopa, levodopa, levothyroxine, tetracyclines, and quinolones.
  • Girls who have started menstruating.
  • Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
  • Allergic to turmeric (natural dye used in placebo).
  • Allergy to prilocaine/lidocaine, if the participant requires it for procedures
  • The onset of sleep symptoms was related to the onset of puberty.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01745497

Locations
United States, Colorado
Childrens Hospital Colorado
Aurora, Colorado, United States, 80045
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G1X8
Sponsors and Collaborators
University of Colorado, Denver
Autism Treatment Network
Massachusetts General Hospital
The EMMES Corporation
Health Resources and Services Administration (HRSA)
Investigators
Principal Investigator: Ann Reynolds, MD Childrens Hospital Colorado
  More Information

Publications:

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01745497     History of Changes
Other Study ID Numbers: 12-0466
Study First Received: November 13, 2012
Last Updated: April 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Autism Spectrum Disorder
Insomnia

Additional relevant MeSH terms:
Autistic Disorder
Sleep Disorders
Parasomnias
Sleep Initiation and Maintenance Disorders
Child Development Disorders, Pervasive
Mental Disorders Diagnosed in Childhood
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias

ClinicalTrials.gov processed this record on August 28, 2014