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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of North Carolina, Chapel Hill
Sponsor:
Information provided by (Responsible Party):
Raj Kasthuri, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01027663
First received: December 4, 2009
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Iron Deficiency Anemia
Malaria
Dietary Supplement: Iron Supplement

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Impact of Host Iron Status and Iron Supplement Use on Growth and Viability of the Erythrocytic Stage of Plasmodium Falciparum

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Estimated Enrollment: 45
Study Start Date: November 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Iron Deficiency Anemia
No Intervention: Hereditary Hemochromatosis
Active Comparator: Iron Supplements 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.

  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: NCT01027663

Contacts
Contact: Raj Kasthuri, MD 919-843-6811 kasthuri@med.unc.edu
Contact: Carla Hand, MD/PhD 919-843-4132 cchand@email.unc.edu

Locations
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Raj Kasthuri, MD    919-843-6811    kasthur@med.unc.edu   
Contact: Carla Hand, MD/PhD    919-843-4384    cchand@email.unc.edu   
Principal Investigator: Raj Kasthuri, MD         
Sub-Investigator: Carla Hand, MD/PhD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Raj Kasthuri, MD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Raj Kasthuri, MD, Assistant Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01027663     History of Changes
Other Study ID Numbers: 09-0559
Study First Received: December 4, 2009
Last Updated: January 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
anemia
malaria

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

ClinicalTrials.gov processed this record on July 26, 2014