Iron DeficiencyMIANCT01156896
Malaria and the Safety of Iron Supplements and Iron Fortification
A study testing Ferrous sulfate in people with Iron Deficiency, run by Columbia University at 1 site in Thailand.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Iron Deficiency
- What is being tested?
- Ferrous sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteThailand
- Study dates
- Jul 2010to Jul 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Hospital for Tropical Diseases, Mahidol University
Bangkok, 10400
About this study
Official title: Malaria and Iron Intervention Safety: Absorption and NTBI
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.
Read the detailed description
This research will determine the effects of acute infection with Plasmodium falciparum on the absorption, pharmacokinetics and metabolism of iron from iron supplements and other iron preparations in non-immune adults in Thailand. Our project will combine measurements of iron absorption during and after successful treatment of acute uncomplicated falciparum malaria with characterization of the pharmacokinetics of the appearance of plasma nontransferrin-bound iron (NTBI) and measurements of the iron regulatory hormone, hepcidin, and other proteins of iron metabolism. We will examine iron supplements like those used in the Pemba supplementation trial (Sazawal et al., Lancet 2006; 367, 133-143) as well as alternative iron interventions that could minimize or avoid the formation of plasma non-transferrin-bound iron. This research has three specific aims:
- to characterize the pharmacokinetics of the appearance of non-transferrin bound iron in the systemic circulation after oral administration of an iron supplement or other iron intervention;
- to determine the effect of acute uncomplicated falciparum malaria on absorption of iron from iron supplements and other iron interventions, using erythrocyte incorporation of stable isotopes of iron;
- to assess the effects of acute uncomplicated falciparum malaria on iron metabolism by repeated measurements of serum hepcidin, transferrin receptor, ferritin, haptoglobin, and concentrations of pro- (Th-1) and anti- (Th-2) inflammatory cytokines, erythrocyte zinc protoporphyrin, and the complete blood count with absolute reticulocyte count and reticulocyte hemoglobin content (CHr).
These studies of the effects of infection with P. falciparum on iron absorption and metabolism will further our basic understanding of the interaction of iron supplements with malaria and other infections. The results could help guide the choice of optimal means for the prevention and treatment of iron deficiency in regions endemic for malaria. Characterization of the pharmacokinetics of changes in plasma iron produced by administration of conventional iron supplements could lead to the design and development of new formulations of supplemental iron that would maximize iron absorption while minimizing risks associated with non-transferrin-bound plasma iron. Because of the public health importance of assuring iron sufficiency in mothers, our studies are focused on women of childbearing age but the results should be broadly applicable to the optimal means of providing iron to infants and children.
- Conditions
- Iron Deficiency
- Being tested
- Ferrous sulfate
- Keywords
- Non-transferrin-bound iron, Iron stable isotopes, Iron deficiency, Malaria, Iron supplementation, Iron fortification
- Medical subject headings
- Iron Deficiencies, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferrous sulfateDietary supplement
Ferrous sulfate, ~1 mg Fe/kg body weight, given as a single dose in the fasting state.
Ferrous sulfateDietary supplement
Ferrous sulfate, ~1 mg Fe/kg body weight, given as a single dose with a standard Thai rice meal.
Ferrous sulfateDietary supplement
Ferrous sulfate, ~1 mg Fe/kg body weight, given as a single dose with a standard Thai rice meal with added oil.
Ferrous sulfateDietary supplement
Ferrous sulfate, ~0.1 mg Fe/kg body weight, given as a single dose with a standard Thai rice meal.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Ferrous sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma non-transferrin-bound iron (NTBI)
After administration of an iron intervention, plasma non-transferrin-bound iron pharmacokinetics will be determined.
Measured: 0, 2, 4, 8, 12 and 24 hours
Secondary outcomes (2)
Erythrocyte 58Fe incorporation
Erythrocyte 58Fe incorporation will be measured using stable-isotope techniques.
Measured: Determined 2 weeks after iron intervention
Fractional 57Fe absorption
Fractional 57Fe absorption will be measured using stable-isotope techniques
Measured: Determined 2 weeks after iron intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionJul 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Iron DeficiencyStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Gary M Brittenham, MD, Columbia University
- Investigators
- Gary M. Brittenham, M.D., Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01156896
- Sponsor's protocol ID
- AAAF0995
- Other IDs
- U01HD061233-04
- Acronym
- MIA
- Status last verified
- Feb 2015
- First submitted
- 2 Jul 2010
- Last updated
- 12 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Malaria and Iron Intervention Safety: Absorption and NTBI
- ClinicalTrials.gov ID
- NCT01156896
- Acronym / sponsor ID
- MIA / AAAF0995
- Conditions
- Iron Deficiency
- Keywords
- Non-transferrin-bound iron, Iron stable isotopes, Iron deficiency, Malaria, Iron supplementation, Iron fortification
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jul 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 5 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This research will determine the effects of acute infection with Plasmodium falciparum on the absorption, pharmacokinetics and metabolism of iron from iron supplements and other iron preparations in non-immune adults in Thailand. Our project will combine measurements of iron absorption during and after successful treatment of acute uncomplicated falciparum malaria with characterization of the pharmacokinetics of the appearance of plasma nontransferrin-bound iron (NTBI) and measurements of the iron regulatory hormone, hepcidin, and other proteins of iron metabolism. We will examine iron supplements like those used in the Pemba supplementation trial (Sazawal et al., Lancet 2006; 367, 133-143) as well as alternative iron interventions that could minimize or avoid the formation of plasma non-transferrin-bound iron. This research has three specific aims:
- to characterize the pharmacokinetics of the appearance of non-transferrin bound iron in the systemic circulation after oral administration of an iron supplement or other iron intervention;
- to determine the effect of acute uncomplicated falciparum malaria on absorption of iron from iron supplements and other iron interventions, using erythrocyte incorporation of stable isotopes of iron;
- to assess the effects of acute uncomplicated falciparum malaria on iron metabolism by repeated measurements of serum hepcidin, transferrin receptor, ferritin, haptoglobin, and concentrations of pro- (Th-1) and anti- (Th-2) inflammatory cytokines, erythrocyte zinc protoporphyrin, and the complete blood count with absolute reticulocyte count and reticulocyte hemoglobin content (CHr).
These studies of the effects of infection with P. falciparum on iron absorption and metabolism will further our basic understanding of the interaction of iron supplements with malaria and other infections. The results could help guide the choice of optimal means for the prevention and treatment of iron deficiency in regions endemic for malaria. Characterization of the pharmacokinetics of changes in plasma iron produced by administration of conventional iron supplements could lead to the design and development of new formulations of supplemental iron that would maximize iron absorption while minimizing risks associated with non-transferrin-bound plasma iron. Because of the public health importance of assuring iron sufficiency in mothers, our studies are focused on women of childbearing age but the results should be broadly applicable to the optimal means of providing iron to infants and children.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Iron intervention | Experimental | Dietary Supplement: Ferrous sulfateAll 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ferrous sulfateFerrous sulfate, ~1 mg Fe/kg body weight, given as a single dose in the fasting state. | Dietary supplement | Iron intervention |
| Ferrous sulfateFerrous sulfate, ~1 mg Fe/kg body weight, given as a single dose with a standard Thai rice meal. | Dietary supplement | Iron intervention |
| Ferrous sulfateFerrous sulfate, ~1 mg Fe/kg body weight, given as a single dose with a standard Thai rice meal with added oil. | Dietary supplement | Iron intervention |
| Ferrous sulfateFerrous sulfate, ~0.1 mg Fe/kg body weight, given as a single dose with a standard Thai rice meal. | Dietary supplement | Iron intervention |
Primary outcome
Plasma non-transferrin-bound iron (NTBI)
Time frame: 0, 2, 4, 8, 12 and 24 hours
After administration of an iron intervention, plasma non-transferrin-bound iron pharmacokinetics will be determined.
2 secondary outcomes
Erythrocyte 58Fe incorporation
Time frame: Determined 2 weeks after iron intervention
Fractional 57Fe absorption
Time frame: Determined 2 weeks after iron intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary M. Brittenham, M.D. principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferrous sulfate in people with Iron Deficiency, run by Columbia University at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma non-transferrin-bound iron (NTBI) (time frame: 0, 2, 4, 8, 12 and 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2015.