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Impact of Host Iron Status and Iron Supplement Use on Erythrocytic Stage of Plasmodium Falciparum

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ClinicalTrials.gov Identifier: NCT01027663
Recruitment Status : Completed
First Posted : December 9, 2009
Last Update Posted : August 8, 2016
Sponsor:
Information provided by (Responsible Party):
Raj Kasthuri, MD, University of North Carolina, Chapel Hill

Tracking Information
First Submitted Date  ICMJE December 4, 2009
First Posted Date  ICMJE December 9, 2009
Last Update Posted Date August 8, 2016
Study Start Date  ICMJE November 2009
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Host Iron Status and Iron Supplement Use on Erythrocytic Stage of Plasmodium Falciparum
Official Title  ICMJE Impact of Host Iron Status and Iron Supplement Use on Growth and Viability of the Erythrocytic Stage of Plasmodium Falciparum
Brief Summary

The purpose of this study is to perform laboratory based studies to determine if the growth and development of the malaria parasite is effected by iron status of its host (the person infected with the malaria parasite). Iron deficiency affects over 500 million people including many pregnant women and children from areas of the world that are plagued by malaria. Some population based studies have suggested that iron deficiency protects people from getting malaria and this has raised questions about the wisdom of public health policies that provide universal iron supplementation in countries where malaria is common. We will use red blood cells and sera from patients with iron deficiency anemia, hereditary hemochromatosis and normal individuals who are taking iron supplements to look at this question in a very systematic way. This study should provide information for or against a possible mechanism by which iron deficiency may affect the malaria parasite. The results will contribute to efforts to develop evidence-based public health policies on iron supplementation policies in malaria-endemic areas.

There are three different types of individuals involved in this study (1) people with iron deficiency anemia who will be taking iron supplementation (2) people without iron deficiency anemia who will be taking iron supplementation and (3) people with a condition called hereditary hemochromatosis who have an excess of iron in their bodies.

Detailed Description

Purpose: This proposal is aimed at studying the effect of an individual's iron status and iron supplementation on the growth and viability of the malarial parasite Plasmodium falciparum. The overall goal is to provide evidence to support the development of evidence-based programs to improve global health policy on iron supplementation in areas of the world with high malaria transmission. Current WHO recommendations include routine supplementation of women and children. Recently however, the wisdom of this policy when applied to areas afflicted with high rates of malaria has come under scrutiny. This proposal will study the effects of red blood cells (RBCs) and sera from iron overloaded patients (with hereditary hemochromatosis), iron deficient patients, and iron replete individuals taking oral iron supplements. This proposal will attempt to identify the mechanism by which the human host's iron status and iron supplement use affects the growth and viability of the P. falciparum parasite in red blood cells.

Participants: Healthy adult volunteers, adults with iron deficiency anemia, and patients with hereditary hemochromatosis will be enrolled in this study. Fifteen individuals will be recruited under each of the above three settings. This study involves only subjects over 18 years of age and both males and females will be included.

Procedures (methods): Participation in the study involves undergoing a series of screening tests and donation of blood and either a single time point (for hemochromatosis patients) or a total of three pre-specified time points (for healthy volunteers and those with iron deficiency). The healthy individuals will be asked to take oral iron supplements once daily (325 mg ferrous sulfate) for the duration of this study. Patient's blood will be separated by centrifugation into RBCs and sera, both of which will be used for in vitro studies on the impact of iron status on the growth and viability of Plasmodium falciparum.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Iron Deficiency Anemia
  • Malaria
Intervention  ICMJE Dietary Supplement: Iron Supplement
Iron supplementation (325 mg of ferrous sulfate) once daily for the 2 month duration of the study.
Other Name: Ferrous sulfate
Study Arms  ICMJE
  • No Intervention: Iron Deficiency Anemia
  • No Intervention: Hereditary Hemochromatosis
  • Active Comparator: Iron Supplements
    Intervention: Dietary Supplement: Iron Supplement
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December¬†8,¬†2009)
45
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

All study participants will need to meet the following eligibility criteria for participation in the study:

  1. 18 years of age or older
  2. Agree to HIV testing
  3. No known malignancy
  4. Agree to pregnancy testing (when applicable)
  5. Do not have sickle cell disease or trait
  6. Do not have thalassemia or thalassemia trait
  7. Not taking iron supplementation
  8. Have O+ or A+ blood group, and
  9. Consent to participate in the study

In addition to the above common study screening tests, additional specific eligibility criteria for the three study groups are as follows:

  1. Individuals with iron deficiency:

    Iron deficiency will be diagnosed using the biochemical parameters listed below

    • Serum iron: <40 µg/dL
    • Iron binding capacity (transferrin): <40 µg/dL
    • Saturation (SI/TIBC): <10 percent
    • Hemoglobin: < 9 g/dL
    • Red cell morphology: Hypochromia and microcytosis
    • Plasma or serum ferritin: <10 ng/mL
  2. Individuals with Hereditary Hemochromatosis (HH):

    In addition to confirmation with genetic testing, it is expected that patients with HH will have the biochemical parameters listed below. From the genotype standpoint, only patients homozygous for the C282Y and H63D mutations and those that are compound heterozygotes for C282Y/H63D will be enrolled. These are the mutations most associated with iron overload in HH patients. Note that we will have different criteria for men and women. Since women (with and without hemochromatosis) have greater iron losses (secondary to menstruation) in comparison to men, they usually have lower iron stores, lower ferritin levels and lower iron saturation.

    Biochemical parameters:

    • Biochemical markers for patients with HH
    • Serum iron: >65 µg/dL
    • Saturation (SI/TIBC): > 60% men; >50% women
    • Plasma or serum ferritin: >300ng/mL men; >200 ng/mL women

    Each study participant will have been diagnosed (via genetic testing) with HH prior to the enrollment.

  3. Healthy volunteers:

Exclusion Criteria:

Patients with HIV, that are pregnant, and those with Sickle cell anemia/trait or Thalassemia/Thal trait will not be eligible to participate in this study as these conditions could interfere with the outcomes of the in vitro studies performed in this proposal.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01027663
Other Study ID Numbers  ICMJE 09-0559
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Raj Kasthuri, MD, University of North Carolina, Chapel Hill
Study Sponsor  ICMJE University of North Carolina, Chapel Hill
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Raj Kasthuri, MD University of North Carolina, Chapel Hill
PRS Account University of North Carolina, Chapel Hill
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP