Acute vs. Delayed Iron Therapy: Effect on Iron Status, Anemia and Cognition

Study Overview
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Brief Summary
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The research questions to be answered by this study are: Is treatment with iron more effective at improving anemia if given at the time of a malaria episode or 1 month after the episode? Which treatment timing is associated with more malaria episodes - 1 month delayed treatment or immediate treatment at the time of malaria? Does timing of iron treatment affect later thinking processes and behavior?

Detailed Description
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The study population in this study will be children who are enrolled in our ongoing study of cerebral malaria and severe malarial anemia, Pathogenesis of cognitive/neurologic deficits in central nervous system malaria, underway in Kampala, Uganda. The pathogenesis study seeks to address the question of why children with severe malaria have later problems in thinking. The study we are now proposing will build on this study by assessing whether children with severe malaria have iron deficiency, and if they do, whether treatment with iron at the time of malaria is less effective than treatment one month later. We believe that treatment one month later may be more effective because there is data that shows that the inflammation that occurs with a malaria episode may decrease the body's ability to absorb iron in the gut and to send iron to the places it is needed, like the bone marrow and the brain. We are doing this study to see if our hypothesis about more effective iron treatment if it is delayed is correct and assessing anemia prevalence, iron status, and long-term neurobehavioral development as outcomes. We have three study groups: children with cerebral malaria, children with severe malarial anemia, and healthy community control children. Children found to be iron deficient will be randomized to receive iron (as ferrous sulphate syrup) either immediately or at their one-month follow-up visit. At 1-, 6, and 12-month follow-up visits changes in iron and inflammation indicators will be assessed. At the 6- and 12-month visits, neurocognitive behavior will also be evaluated and compared between the immediate vs. delayed iron groups. Malaria morbidity will be assessed via home visits during the period of iron supplementation and via clinic monitoring for the duration of the study.

Official Title
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Acute vs. Delayed Iron Therapy: Effect on Iron Status, Anemia and Cognition

Conditions
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Anemia, Inflammation, Malaria Morbidity, Cognitive Development

Intervention / Treatment
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* Dietary Supplement: Ferrous Sulphate Syrup


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All children must Be between the ages of 18 mo and 5 y Reside within 20 km of study hospital Children with cerebral malaria must have Coma (BCS < 3) P. falciparum on blood smear No clinical evidence or other causes of encephalopathy Children with severe malarial anemia must have Hemoglobin < 5 g/dL Clinical symptoms of malaria P. falciparum on blood smear Community control children must Live in same neighborhood or extended household as a child with severe malaria Be within one year of age as a child with severe malaria Exclusion Criteria: Cerebral malaria WBC > 10 Positive gram stain or culture Severe malarial anemia Impaired conscious on physical exam Seizure activity prior to or during physical exam Any other evidence of CNS disease All exclusion criteria of CM except no lumbar puncture required Community control children All exclusion criteria for CM Any active illness, recent illness, or recovery from illness Chronic illness requiring medical care Medical abnormalities on screening history of physical exam CC control with a positive malaria smear will be treated but will not be excluded from the study.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Immediate iron<br>Iron-deficient children will be randomized to receive iron concurrently with anti-malarial treatment or one month later (delayed iron group). | Dietary Supplement: Ferrous Sulphate Syrup<br>* Iron therapy will consist of a three-month course of ferrous sulphate syrup. For children with Hb ≥ 7 g/dL, each daily dose will be based on 2 mg iron/kg body weight.<br>|
| Active Comparator: Delayed iron<br> | Dietary Supplement: Ferrous Sulphate Syrup<br>* Iron therapy will consist of a three-month course of ferrous sulphate syrup. For children with Hb ≥ 7 g/dL, each daily dose will be based on 2 mg iron/kg body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin change, anemia prevalence, and socioemotional behavior in the immediate iron vs. delayed iron groups |  | 6 months |