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

Primary Purpose

Iron Deficiency Anemia, Malaria

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Iron Supplement

About this trial

This is an interventional basic science trial for Iron Deficiency Anemia focused on measuring anemia, malaria

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

18 years of age or older
Agree to HIV testing
No known malignancy
Agree to pregnancy testing (when applicable)
Do not have sickle cell disease or trait
Do not have thalassemia or thalassemia trait
Not taking iron supplementation
Have O+ or A+ blood group, and
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:

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
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.
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.

Sites / Locations

University of North Carolina at Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Active Comparator

Arm Label

Iron Deficiency Anemia

Hereditary Hemochromatosis

Iron Supplements

Arm Description

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

NCT ID

NCT01027663

First Posted

December 4, 2009

Last Updated

August 5, 2016

Sponsor

University of North Carolina, Chapel Hill

1. Study Identification

Unique Protocol Identification Number

NCT01027663

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of North Carolina, Chapel Hill

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Iron Deficiency Anemia, Malaria

Keywords

anemia, malaria

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

45 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Iron Deficiency Anemia

Arm Type

No Intervention

Arm Title

Hereditary Hemochromatosis

Arm Type

No Intervention

Arm Title

Iron Supplements

Arm Type

Active Comparator

Intervention Type

Dietary Supplement

Intervention Name(s)

Iron Supplement

Other Intervention Name(s)

Ferrous sulfate

Intervention Description

Iron supplementation (325 mg of ferrous sulfate) once daily for the 2 month duration of the study.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All study participants will need to meet the following eligibility criteria for participation in the study: 18 years of age or older Agree to HIV testing No known malignancy Agree to pregnancy testing (when applicable) Do not have sickle cell disease or trait Do not have thalassemia or thalassemia trait Not taking iron supplementation Have O+ or A+ blood group, and 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: 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 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raj Kasthuri, MD

Organizational Affiliation

University of North Carolina, Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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

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