Impact of Iron Supplementation Treatment on Brain Iron Concentrations

Impact of Iron Supplementation Treatment on Brain Iron Concentrations Among Children With ADHD & Restless Leg Syndrome Combined With Periodic Limb Movements in Sleep

The goal of the present study is to provide novel data to evaluate brain iron concentration as a mediator of the association between iron supplementation treatment and improvement in symptoms of ADHD and RLS in children, including PLMS. Twelve participants between the ages of 10 and 15 years will be recruited via Kennedy Krieger Institute's Sleep Disorders Clinic. Eligible participants will be asked to complete, at baseline (pre-iron supplementation treatment) and again at follow-up (post-treatment): 1) a 7 Tesla MRI scan, 2) five consecutive nights of RestEaZe™ monitoring, 3) caregiver-reported (or patient-reported if over the age of 10 years) International Restless Leg Syndrome Scale (IRLSS), and 4) caregiver-reported ADHD Rating Scale-5. The treatment interval will be 3 months.

Study Overview

• Status: Recruiting
• Conditions: Restless Legs Syndrome; Iron-deficiency; ADHD; Periodic Limb Movement Sleep Disorder
• Intervention / Treatment: Dietary supplement: ferrous sulfate

Detailed Description

The goal of the present study is to provide novel data to evaluate brain iron concentration as a mediator of the association between iron supplementation treatment and improvement in symptoms of ADHD and RLS in children, including PLMS. Aim 1 is to evaluate the impact of iron supplementation treatment on peripheral iron concentrations and brain iron concentrations. The investigators hypothesize that iron supplementation treatment will result in increased peripheral and brain iron concentrations. Aim 2 is to evaluate the impact of iron supplementation treatment on symptoms of ADHD and restlessness during sleep. The investigators hypothesize that iron supplementation treatment will result in decreased symptoms of ADHD and restlessness during sleep. Aim 3 is to investigate the relation between brain iron concentrations and symptoms of ADHD and restlessness during sleep, including PLMS. The investigators hypothesize that brain iron concentrations in the substantia nigra and in the thalamus will be negatively related to symptoms at baseline. Aim 4 is to evaluate whether brain iron concentrations mediate the association between iron supplementation treatment and symptoms of ADHD and restlessness during sleep. The investigators hypothesize that increases in brain iron concentrations in the substantia nigra and in the thalamus will fully explain any improvements in symptoms that occur with iron supplementation treatment.

Twelve participants between the ages of 10 and 15 years will be recruited via Kennedy Krieger Institute's Sleep Disorders Clinic. Recruitment will be accomplished by posting flyers with study information at the clinic and by asking Sleep Disorders Clinic clinicians to discuss the study with their patients who may be eligible and their caregivers. In order to be included in the study, participants will need to have: 1) a clinical diagnosis of ADHD, 2) parent or patient self report of restless sleep, 3) serum iron values with ferritin < 50 mcg/L . Exclusionary criteria will be: 1) family is not proficient in English language, 2) child is in foster care, 3) child has a chronic medical condition or genetic/metabolic disorder that might impact iron metabolism, 4) child has another sleep disorder or neuropsychiatric condition that might influence sleep, RLS, or ADHD symptoms, and 6) child has been receiving iron supplementation or a medication that could disrupt sleep.

An uncontrolled open label trial design is proposed for this pilot study, in order to establish evidence to support a larger blinded, placebo-controlled trial application. Eligible participants will be asked to complete, at baseline (pre-iron supplementation treatment) and again at follow-up (post-treatment): 1) a 7 Tesla MRI scan, 2) five consecutive nights of RestEaZe™ monitoring, 3) caregiver-reported or patient-reported if over the age of 10 years International Restless Leg Syndrome Scale (IRLSS), and 4) caregiver-reported ADHD Rating Scale-5. The treatment interval will be 3 months, which has been sufficient in previous studies to allow for treatment effects to be observed. Investigators anticipate 20 to 30% attrition over the course of the 3 months of treatment, leaving 8-10 participants to scan at follow-up.

• Study Type: Observational
• Enrollment (Estimated): 12

Contacts and Locations

• Study Contact: Name: Alison E Pritchard, PhD; Phone Number: 443-923-4409; Email: pritchard@kennedykrieger.org

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Kennedy Krieger Institute
      • Contact: Alison Pritchard, PhD; Phone Number: 443-923-4409; Email: pritchard@kennedykrieger.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Twelve participants between the ages of 5 and 18 years will be recruited via Kennedy Krieger Institute's Sleep Disorders Clinic. Recruitment will be accomplished by posting flyers with study information at the clinic and by asking Sleep Disorders Clinic clinicians to discuss the study with their patients who may be eligible and their caregivers.

Description

Inclusion Criteria:

• a clinical diagnosis of RLS
• a clinical diagnosis of ADHD
• PLMS > 3/hour, based on average of 5 nights of home recording with RestEaze leg meters
• fasting serum iron values with ferritin < 50 mcg/kg and transferrin saturation < 45%

Exclusion Criteria:

• family is not proficient in English language
• child is in foster care
• child has a chronic medical condition or genetic/metabolic disorder that might impact iron metabolism
• child has another sleep disorder or neuropsychiatric condition that might influence sleep, RLS, or ADHD symptoms
• child has been receiving iron supplementation, psychostimulant treatment, or a dopamine agonist within the past 6 months.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ADHD+RLS; Twelve participants between the ages of 5 and 18 years with a clinical diagnosis of either RLS or ADHD, and iron deficiency.

Dietary supplement: ferrous sulfate; Although established guidelines do not currently exist for iron supplementation for children, studies have demonstrated effectiveness of a 3-month treatment regimen of 5mg/kg per day of orally-administered ferrous sulfate in reducing PLMS and subjective RLS symptoms and in increasing serum ferritin levels. Ferrous sulfate 80 mg/day resulted in improvement of ADHD symptoms in iron-deficient children.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ADHD symptoms	Change in ADHD symptoms measured by parent-reported ADHD-RS-V	Change from pre- to post- 3 months of iron supplementation treatment
Change in RLS symptoms	Change in RLS symptoms measured by and RestEaZe™ monitors	Change from pre- to post- 3 months of iron supplementation treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain-based iron concentrations	Change in brain-based iron concentrations indexed by 7 Tesla MRI scans	Change from pre- to post- 3 months of iron supplementation treatment
Change in blood-based iron concentrations	Change in blood-based iron concentrations indexed by ferritin and transferrin	Change from pre- to post- 3 months of iron supplementation treatment

Collaborators and Investigators

• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• Investigators: Principal Investigator: Alison E Pritchard, PhD, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 27, 2019
• First Submitted That Met QC Criteria: October 28, 2019
• First Posted (Actual): October 30, 2019

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Metabolic Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Iron Metabolism Disorders; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Sleep Wake Disorders; Psychomotor Agitation; Restless Legs Syndrome; Iron Deficiencies
• Other Study ID Numbers: KKI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Unknown at this time

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No