Clinical trial NCT04144790: Impact of Iron Supplementation Treatment on Brain Iron Concentrations
Official title: Impact of Iron Supplementation Treatment on Brain Iron Concentrations Among Children With ADHD & Restless Leg Syndrome Combined With Periodic Limb Movements in Sleep
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: ADHD
Iron-deficiency
Restless Legs Syndrome
Periodic Limb Movement Sleep Disorder
Lead sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor class: OTHER
First posted: 2019-10-30
Enrollment: 12
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in ADHD symptoms
timeFrame: Change from pre- to post- 3 months of iron supplementation treatment
measure: Change in RLS symptoms
timeFrame: Change from pre- to post- 3 months of iron supplementation treatment
Secondary outcomes:
measure: Change in brain-based iron concentrations
timeFrame: Change from pre- to post- 3 months of iron supplementation treatment
measure: Change in blood-based iron concentrations
timeFrame: Change from pre- to post- 3 months of iron supplementation treatment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
Study officials:
affiliation: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
name: Alison E Pritchard, PhD
role: PRINCIPAL_INVESTIGATOR
References: