Acute vs. Delayed Iron: Effect on Red Cell Iron Incorporation in Severe Malaria

Malaria Clinical Trial

Official title:

Acute vs. Delayed Iron: Effect on Red Cell Iron Incorporation in Severe Malaria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01754701
• Other study ID #: 1203M11234
• Secondary ID: 1R03HD074262
• Status: Completed
• Phase: N/A
• First received: December 18, 2012
• Last updated: November 25, 2015
• Start date: June 2013
• Est. completion date: May 2015

Study information

• Verified date: November 2015
• Source: University of Minnesota - Clinical and Translational Science Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUganda: Research Ethics CommitteeUganda: National Council for Science and TechnologyUganda: National Drug Authority
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether iron therapy given to iron-deficient Ugandan children with moderate-to-severe anemia and clinical malaria is better absorbed and incorporated into red blood cells if it is given concurrently with antimalarial treatment on Day 0 (immediate group) or 4 weeks after antimalarial treatment on Day 28 (delayed group). Use of iron stable isotopes 57Fe and 58Fe will permit measurement of red blood cell iron incorporation on Day 0 and Day 28 in all children. The investigators hypothesize that red cell iron incorporation at the time of initial supplement administration will be greater in children receiving delayed vs. immediate iron (Aim 1), and children in the delayed group will also have greater hematological recovery on Day 56 than children in the immediate group (Aim 2).

Description:

Approximately 1 million children < 5 y living in sub-Saharan Africa die from severe anemia annually. This severe anemia frequently results from coexisting iron deficiency and malaria infection, but the standard of care, concurrent iron therapy and antimalarial treatment, has proven ineffective at curing the profound anemia and has promoted proliferation of the parasite in some studies. The pro-inflammatory immune response mounted against malaria down-regulates iron absorption in the gut, making provision of oral iron supplements during malarial infection of questionable utility. The present study proposes to use iron stable isotopes and a randomized design to test whether starting 4 weeks of iron therapy immediately after antimalarial treatment or 4 weeks later is associated with greater iron incorporation into red blood cells at the time of initial administration of iron therapy and improved long-term hematological recovery. One hundred severely anemic (hemoglobin 5-9.9 g/dL) Ugandan children 6-59 mos with clinical signs of malaria who present to the Pediatric Acute Care Ward of Mulago Hospital in Kampala, Uganda, will be randomized to start iron immediately after antimalarial treatment on Day 0 (immediate group) or 4 weeks later on Day 28 (delayed group). Children will be assessed at the hospital on Day 0, Day 28 and Day 56 and will receive bi-weekly home visits for the 56-day study duration. The specific aims and corresponding hypotheses of the proposed study are:

Aim 1: Identify the sequencing of antimalarial treatment and iron therapy that results in the greatest red cell iron incorporation at the time of initial iron supplement administration. The working hypothesis is that red cell iron incorporation will be greater at the time of initial supplement administration in children starting iron 4 weeks after antimalarial treatment (delayed group) compared to children starting iron concurrently with antimalarial treatment (immediate group), due to more complete parasite clearance and resolution of inflammation, permitting better iron uptake, distribution, and utilization.

Aim 2: Determine whether long-term hematological recovery is impacted by immediate vs. delayed iron. The working hypothesis is that delayed iron treatment will be associated with greater hemoglobin and improved iron status at Day 56 compared to immediate treatment due to more complete parasite clearance and consequent improved iron absorption and use in the delayed group.

The results of this study will establish a physiologically-based framework for the optimal timing of antimalarial treatment and iron therapy upon which future interventions aimed at improving iron status in malaria-endemic regions can be built, thus helping to reduce the morbidity and mortality and ensure the full neurobehavioral development of the millions of severely anemic children suffering from iron-deficiency and malaria.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 59 Months

Eligibility

Inclusion Criteria:

1. 6 - 59 months of age

2. Hemoglobin 5.0 - 9.9 g/dL according to HemoCue

3. Temperature > 37.5°C or history of fever in past 24 hours

4. P. falciparum on blood smear at Acute Care Unit

5. Residence<50 km of study hospital

Exclusion Criteria:

1. Impaired consciousness on physical exam or history of coma with present illness

2. Seizure activity prior to or during admission

3. Known sickle cell disease 4) Acute malnutrition

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Global Health
• Iron Deficiency
• Malaria
• Nutrition

Intervention

Dietary Supplement:
• Immediate iron
Children who start 4 weeks of iron therapy on Day 0
• Delayed iron
Children who start 4 weeks of iron therapy on Day 28

Locations

Country	Name	City	State
Uganda	Mulago Hospital	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota - Clinical and Translational Science Institute	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent red blood cell iron incorporation on Day 0 in children in the immediate group vs. percent red blood cell iron incorporation on Day 28 in children in the delayed group	All children will receive iron stable isotope 57Fe on Day 0 and iron stable isotope 58Fe on Day 28. Children in the immediate group will begin 27 days of daily iron syrup at home on Day 1. Children in the delayed group will begin 27 days of daily iron syrup at home on Day 29. All children will be assessed at the hospital at Day 28 and Day 56.	56 days	No
Secondary	Hematological recovery in the immediate vs. delayed groups on Day 56	All children will receive iron stable isotope 57Fe on Day 0 and iron stable isotope 58Fe on Day 28. Children in the immediate group will begin 27 days of daily iron syrup at home on Day 1. Children in the delayed group will begin 27 days of daily iron syrup at home on Day 29. All children will be assessed at the hospital at Day 28 and Day 56.	56 days	No