Iron Treatment of Sleep Disorders in Children With Autism Spectrum Disorder

NCT01745497 | Completed Phase 2 DMC

• 1 other identifier: 12-0466
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Autism Spectrum Disorder; Insomnia

Keywords

Autism Spectrum Disorder; Insomnia

Outcome Measures

Primary Outcomes (1)

• Improvement in sleep onset

  Improvement in sleep onset latency will be measured using actigraphy before and after treatment with iron vs placebo.

  3 month

Secondary Outcomes (2)

• Changes inDay time behavior

  3 months

• Improvements in sleep maintenance insomnia

  3 months

Study Arms (2)

Ferrous Sulfate

EXPERIMENTAL

3mg/kg divided twice per day, 30 minutes before a meal or 2 hours after a meal

Drug: Ferrous sulfate

Placebo

PLACEBO COMPARATOR

Equivalent volume of liquid placebo administered twice daily, before a meal or 2 hours after a meal

Drug: Placebo

Interventions

Ferrous sulfate DRUG

3mg/kg liquid

Also known as: Fer-in-Sol

Ferrous Sulfate

Placebo DRUG

Equivalent volume of liquid with similar color and taste.

Placebo

Eligibility Criteria

• Age: 2 Years - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Autism Treatment Network: collaborator
• Massachusetts General Hospital: collaborator
• The Emmes Company, LLC: collaborator
• Health Resources and Services Administration (HRSA): collaborator

Study Sites (4)

Childrens Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

Related Publications (13)

• Richdale AL, Schreck KA. Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies. Sleep Med Rev. 2009 Dec;13(6):403-11. doi: 10.1016/j.smrv.2009.02.003. Epub 2009 Apr 24.

  PMID: 19398354 RESULT

• Schreck KA, Mulick JA, Smith AF. Sleep problems as possible predictors of intensified symptoms of autism. Res Dev Disabil. 2004 Jan-Feb;25(1):57-66. doi: 10.1016/j.ridd.2003.04.007.

  PMID: 14733976 RESULT

• Picchietti D, Allen RP, Walters AS, Davidson JE, Myers A, Ferini-Strambi L. Restless legs syndrome: prevalence and impact in children and adolescents--the Peds REST study. Pediatrics. 2007 Aug;120(2):253-66. doi: 10.1542/peds.2006-2767.

  PMID: 17671050 RESULT

• Picchietti DL, Walters AS. Moderate to severe periodic limb movement disorder in childhood and adolescence. Sleep. 1999 May 1;22(3):297-300. doi: 10.1093/sleep/22.3.297.

  PMID: 10341379 RESULT

• Reed HE, McGrew SG, Artibee K, Surdkya K, Goldman SE, Frank K, Wang L, Malow BA. Parent-based sleep education workshops in autism. J Child Neurol. 2009 Aug;24(8):936-45. doi: 10.1177/0883073808331348. Epub 2009 Jun 1.

  PMID: 19491110 RESULT

• Bokkala S, Napalinga K, Pinninti N, Carvalho KS, Valencia I, Legido A, Kothare SV. Correlates of periodic limb movements of sleep in the pediatric population. Pediatr Neurol. 2008 Jul;39(1):33-9. doi: 10.1016/j.pediatrneurol.2008.03.008.

  PMID: 18555170 RESULT

• Picchietti MA, Picchietti DL. Advances in pediatric restless legs syndrome: Iron, genetics, diagnosis and treatment. Sleep Med. 2010 Aug;11(7):643-51. doi: 10.1016/j.sleep.2009.11.014.

  PMID: 20620105 RESULT

• Simakajornboon N, Kheirandish-Gozal L, Gozal D. Diagnosis and management of restless legs syndrome in children. Sleep Med Rev. 2009 Apr;13(2):149-56. doi: 10.1016/j.smrv.2008.12.002. Epub 2009 Jan 31.

  PMID: 19186083 RESULT

• Morgenthaler T, Alessi C, Friedman L, Owens J, Kapur V, Boehlecke B, Brown T, Chesson A Jr, Coleman J, Lee-Chiong T, Pancer J, Swick TJ; Standards of Practice Committee; American Academy of Sleep Medicine. Practice parameters for the use of actigraphy in the assessment of sleep and sleep disorders: an update for 2007. Sleep. 2007 Apr;30(4):519-29. doi: 10.1093/sleep/30.4.519.

  PMID: 17520797 RESULT

• Latif A, Heinz P, Cook R. Iron deficiency in autism and Asperger syndrome. Autism. 2002 Mar;6(1):103-14. doi: 10.1177/1362361302006001008.

  PMID: 11918106 RESULT

• Herguner S, Kelesoglu FM, Tanidir C, Copur M. Ferritin and iron levels in children with autistic disorder. Eur J Pediatr. 2012 Jan;171(1):143-6. doi: 10.1007/s00431-011-1506-6. Epub 2011 Jun 4.

  PMID: 21643649 RESULT

• Dosman CF, Drmic IE, Brian JA, Senthilselvan A, Harford M, Smith R, Roberts SW. Ferritin as an indicator of suspected iron deficiency in children with autism spectrum disorder: prevalence of low serum ferritin concentration. Dev Med Child Neurol. 2006 Dec;48(12):1008-9. doi: 10.1017/S0012162206232225. No abstract available.

  PMID: 17109795 RESULT

• Dosman CF, Brian JA, Drmic IE, Senthilselvan A, Harford MM, Smith RW, Sharieff W, Zlotkin SH, Moldofsky H, Roberts SW. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol. 2007 Mar;36(3):152-8. doi: 10.1016/j.pediatrneurol.2006.11.004.

  PMID: 17352947 RESULT

MeSH Terms

Conditions

Autism Spectrum Disorder; Sleep Initiation and Maintenance Disorders

Interventions

ferrous sulfate

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Officials

• Ann Reynolds, MD

  Childrens Hospital Colorado

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: December 10, 2012
• Study Start: December 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: August 3, 2020

Record last verified: 2020-07

Locations

US (3); CA (1)