Malaria and the Safety of Iron Supplements and Iron Fortification

NCT01156896 | Completed

• 2 other identifiers: AAAF0995U01HD061233-04
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

The primary study hypothesis of the investigators is that administration of an iron supplement between meals at a dose like that used in the Pemba trial (\~1 mg Fe/kg) during P. falciparum parasitemia will increase plasma non-transferrin-bound iron. A key subsidiary hypothesis is that iron administered with meals in amounts used in food fortification (\~0.1 mg Fe/kg) will not produce plasma non-transferrin-bound iron. This research will be carried out at the Hospital for Tropical Diseases, Mahidol University, Bangkok, Thailand. The studies are intended to help understand how giving iron and folic acid to preschool children in Pemba, Zanzibar, Tanzania, (the "Pemba trial") in the doses recommended by the World Health Organization, could have resulted in an increase in hospitalizations and deaths. The investigators will examine the most likely explanation, that the dose of iron supplements used in the Pemba trial produced iron in the blood not bound to the usual carrier for iron (a protein called "transferrin"), that is called "non-transferrin-bound iron", abbreviated as NTBI. In children with malaria, this NTBI might favor the growth of malarial parasites or other causes of infection. At present, no studies have been carried out to see if NTBI is present after giving iron to patients with malaria. Using non-radioactive forms of iron (called "stable isotopes"), the investigators will study iron absorption and NTBI after giving a single dose of iron (like that used in the Pemba trial) one day after treatment for malaria has been started, while patients still have malaria parasites in the blood, and then again two weeks later, after the malaria has been cured. The investigators will study adults admitted to the Hospital for Tropical Diseases in Bangkok, Thailand, with malaria. For reasons of safety, the investigators have chosen to study adults in the hospital rather than children living in an area like Pemba but the results should also apply to children. The outcome of this research will help us design ways of safely giving iron in malarious areas to adults and children to prevent or treat iron deficiency.

Conditions

Iron Deficiency

Keywords

Non-transferrin-bound iron; Iron stable isotopes; Iron deficiency; Malaria; Iron supplementation; Iron fortification

Outcome Measures

Primary Outcomes (1)

• Plasma non-transferrin-bound iron (NTBI)

  After administration of an iron intervention, plasma non-transferrin-bound iron pharmacokinetics will be determined.

  0, 2, 4, 8, 12 and 24 hours

Secondary Outcomes (2)

• Erythrocyte 58Fe incorporation

  Determined 2 weeks after iron intervention

• Fractional 57Fe absorption

  Determined 2 weeks after iron intervention

Study Arms (1)

Iron intervention

EXPERIMENTAL

All study subjects with malaria and all control subjects will receive an iron intervention (supplement or fortification dose of iron). Control subjects will be studied on only one occasion. Study subjects with malaria will receive the same iron intervention two weeks later, after the malarial episode has been successfully treated.

Dietary Supplement: Ferrous sulfate

Interventions

Ferrous sulfate DIETARY_SUPPLEMENT

Ferrous sulfate, \~1 mg Fe/kg body weight, given as a single dose in the fasting state.

Iron intervention

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• men or premenopausal woman, 18 to 50 years of age;
• peripheral blood positive for asexual forms of P. falciparum (this criterion not applicable to uninfected healthy control subjects);
• women not pregnant by self-report and not planning pregnancy;
• body weight \<65 kg.

You may not qualify if:

• presence of severe or complicated malaria as defined by WHO criteria;
• clinical evidence of ill health or a history of chronic disorders;
• treatment for mental illness;
• imprisonment;
• institutionalization.

Sponsors & Collaborators

• Columbia University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Hospital for Tropical Diseases, Mahidol University

Bangkok, 10400, Thailand

Location

MeSH Terms

Conditions

Iron Deficiencies; Malaria

Interventions

ferrous sulfate

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Gary M. Brittenham, M.D.

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: James A Wolff Professor of Pediatrics

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 5, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 12, 2015

Record last verified: 2015-02

Locations

TH (1)