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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Minnesota - Clinical and Translational Science Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01754701
First received: December 18, 2012
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

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).


Condition Intervention
Iron Deficiency
Malaria
Nutrition
Global Health
Dietary Supplement: Ferrous sulfate syrup; iron stable isotope 57Fe; iron stable isotope 58Fe

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Acute vs. Delayed Iron: Effect on Red Cell Iron Incorporation in Severe Malaria

Resource links provided by NLM:


Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:
  • 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 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Hematological recovery in the immediate vs. delayed groups on Day 56 [ Time Frame: 56 days ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 100
Study Start Date: June 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Immediate iron
Children who start 4 weeks of iron therapy on Day 0
Dietary Supplement: Ferrous sulfate syrup; iron stable isotope 57Fe; iron stable isotope 58Fe
Experimental: Delayed iron
Children who start 4 weeks of iron therapy on Day 28
Dietary Supplement: Ferrous sulfate syrup; iron stable isotope 57Fe; iron stable isotope 58Fe

Detailed 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.

  Eligibility

Ages Eligible for Study:   6 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01754701

Contacts
Contact: Sarah Cusick, Ph.D. 612-625-8549 scusick@umn.edu

Locations
Uganda
Mulago Hospital Recruiting
Kampala, Uganda
Contact: Andrew Ssemata, M.S.       andrewssemata@yahoo.co.uk   
Principal Investigator: Ezekiel Mupere, MMed, PhD, MS         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Sarah Cusick, Ph.D. University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01754701     History of Changes
Other Study ID Numbers: 1203M11234, 1R03HD074262
Study First Received: December 18, 2012
Last Updated: September 3, 2014
Health Authority: United States: Institutional Review Board
Uganda: Research Ethics Committee
Uganda: National Council for Science and Technology
Uganda: National Drug Authority

Additional relevant MeSH terms:
Protozoan Infections
Anemia, Iron-Deficiency
Malaria
Anemia
Anemia, Hypochromic
Hematologic Diseases
Iron Metabolism Disorders
Metabolic Diseases
Parasitic Diseases
Iron
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Trace Elements

ClinicalTrials.gov processed this record on November 25, 2014