Iron DeficiencyNCT01754701
Acute vs. Delayed Iron: Effect on Red Cell Iron Incorporation in Severe Malaria
A study testing Immediate iron and Delayed iron in people with Iron Deficiency and Malaria, run by University of Minnesota at 1 site in Uganda.
Trial summary
The purpose of this study is to determine whether iron therapy given to iron-deficient Ugandan children with moderate-to-severe anemia and clinical malaria is better absorbed and incorporated into red blood cells if it is given concurrently with antimalarial treatment on Day 0 (immediate group) or 4 weeks after… Read more about this study
- Who is it for?
- Ages 6 to 59 months
- Conditions the study is for
- Iron Deficiency, Malaria, Nutrition
- What is being tested?
- Immediate iron and Delayed iron
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteUganda
- Study dates
- Jun 2013to May 2015
- 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 6 to 59 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 6 - 59 months of age
- Hemoglobin 5.0 - 9.9 g/dL according to HemoCue
- Temperature > 37.5°C or history of fever in past 24 hours
- P. falciparum on blood smear at Acute Care Unit
- Residence<50 km of study hospital
Who cannot join
- Impaired consciousness on physical exam or history of coma with present illness
- Seizure activity prior to or during admission
- Known sickle cell disease 4) Acute malnutrition
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether iron therapy given to iron-deficient Ugandan children with moderate-to-severe anemia and clinical malaria is better absorbed and incorporated into red blood cells if it is given concurrently with antimalarial treatment on Day 0 (immediate group) or 4 weeks after antimalarial treatment on Day 28 (delayed group). Use of iron stable isotopes 57Fe and 58Fe will permit measurement of red blood cell iron incorporation on Day 0 and Day 28 in all children. The investigators hypothesize that red cell iron incorporation at the time of initial supplement administration will be greater in children receiving delayed vs. immediate iron (Aim 1), and children in the delayed group will also have greater hematological recovery on Day 56 than children in the immediate group (Aim 2).
Read the detailed description
Approximately 1 million children < 5 y living in sub-Saharan Africa die from severe anemia annually. This severe anemia frequently results from coexisting iron deficiency and malaria infection, but the standard of care, concurrent iron therapy and antimalarial treatment, has proven ineffective at curing the profound anemia and has promoted proliferation of the parasite in some studies. The pro-inflammatory immune response mounted against malaria down-regulates iron absorption in the gut, making provision of oral iron supplements during malarial infection of questionable utility. The present study proposes to use iron stable isotopes and a randomized design to test whether starting 4 weeks of iron therapy immediately after antimalarial treatment or 4 weeks later is associated with greater iron incorporation into red blood cells at the time of initial administration of iron therapy and improved long-term hematological recovery. One hundred severely anemic (hemoglobin 5-9.9 g/dL) Ugandan children 6-59 mos with clinical signs of malaria who present to the Pediatric Acute Care Ward of Mulago Hospital in Kampala, Uganda, will be randomized to start iron immediately after antimalarial treatment on Day 0 (immediate group) or 4 weeks later on Day 28 (delayed group). Children will be assessed at the hospital on Day 0, Day 28 and Day 56 and will receive bi-weekly home visits for the 56-day study duration. The specific aims and corresponding hypotheses of the proposed study are:
Aim 1: Identify the sequencing of antimalarial treatment and iron therapy that results in the greatest red cell iron incorporation at the time of initial iron supplement administration. The working hypothesis is that red cell iron incorporation will be greater at the time of initial supplement administration in children starting iron 4 weeks after antimalarial treatment (delayed group) compared to children starting iron concurrently with antimalarial treatment (immediate group), due to more complete parasite clearance and resolution of inflammation, permitting better iron uptake, distribution, and utilization.
Aim 2: Determine whether long-term hematological recovery is impacted by immediate vs. delayed iron. The working hypothesis is that delayed iron treatment will be associated with greater hemoglobin and improved iron status at Day 56 compared to immediate treatment due to more complete parasite clearance and consequent improved iron absorption and use in the delayed group.
The results of this study will establish a physiologically-based framework for the optimal timing of antimalarial treatment and iron therapy upon which future interventions aimed at improving iron status in malaria-endemic regions can be built, thus helping to reduce the morbidity and mortality and ensure the full neurobehavioral development of the millions of severely anemic children suffering from iron-deficiency and malaria.
- Conditions
- Iron Deficiency, Malaria, Nutrition, Global Health
- Being tested
- Immediate iron, Delayed iron
- 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.
Immediate ironDietary supplement
Also called Ferrous sulfate syrup
Children who start 4 weeks of iron therapy on Day 0
Delayed ironDietary supplement
Children who start 4 weeks of iron therapy on Day 28
| Study group | Role | What they receive |
|---|---|---|
| Immediate iron | Experimental | Children who start 4 weeks of iron therapy on Day 0 Receives: Dietary Supplement: Immediate iron |
| Delayed iron | Experimental | Children who start 4 weeks of iron therapy on Day 28 Receives: Dietary Supplement: Delayed iron |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent red blood cell iron incorporation on Day 0 in children in the immediate group vs. percent red blood cell iron incorporation on Day 28 in children in the delayed group
All children will receive iron stable isotope 57Fe on Day 0 and iron stable isotope 58Fe on Day 28. Children in the immediate group will begin 27 days of daily iron syrup at home on Day 1. Children in the delayed group will begin 27 days of daily iron syrup at home on Day 29. All children will be assessed at the hospital at Day 28 and Day 56.
Measured: 56 days
Secondary outcomes (1)
Hematological recovery in the immediate vs. delayed groups on Day 56
All children will receive iron stable isotope 57Fe on Day 0 and iron stable isotope 58Fe on Day 28. Children in the immediate group will begin 27 days of daily iron syrup at home on Day 1. Children in the delayed group will begin 27 days of daily iron syrup at home on Day 29. All children will be assessed at the hospital at Day 28 and Day 56.
Measured: 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2012 (estimated)
- Study startJun 2013
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Iron DeficiencyStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Sarah Cusick, Ph.D., Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01754701
- Sponsor's protocol ID
- 1203M11234
- Other IDs
- 1R03HD074262
- Status last verified
- Nov 2015
- First submitted
- 18 Dec 2012
- Last updated
- 30 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cusick SE, Opoka RO, Abrams SA, John CC, Georgieff MK, Mupere E. Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and Equivalent Hematologic Recovery after 56 Days in Children: A Randomized Controlled Trial. J Nutr. 2016 Sep;146(9):1769-74. doi: 10.3945/jn.116.233239. Epub 2016 Jun 29.
PubMed 27358418
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute vs. Delayed Iron: Effect on Red Cell Iron Incorporation in Severe Malaria
- ClinicalTrials.gov ID
- NCT01754701
- Acronym / sponsor ID
- 1203M11234
- Conditions
- Iron Deficiency, Malaria, Nutrition, Global Health
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jun 2013
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 21 Dec 2012 (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 purpose of this study is to determine whether iron therapy given to iron-deficient Ugandan children with moderate-to-severe anemia and clinical malaria is better absorbed and incorporated into red blood cells if it is given concurrently with antimalarial treatment on Day 0 (immediate group) or 4 weeks after antimalarial treatment on Day 28 (delayed group). Use of iron stable isotopes 57Fe and 58Fe will permit measurement of red blood cell iron incorporation on Day 0 and Day 28 in all children. The investigators hypothesize that red cell iron incorporation at the time of initial supplement administration will be greater in children receiving delayed vs. immediate iron (Aim 1), and children in the delayed group will also have greater hematological recovery on Day 56 than children in the immediate group (Aim 2).
Detailed description
Approximately 1 million children < 5 y living in sub-Saharan Africa die from severe anemia annually. This severe anemia frequently results from coexisting iron deficiency and malaria infection, but the standard of care, concurrent iron therapy and antimalarial treatment, has proven ineffective at curing the profound anemia and has promoted proliferation of the parasite in some studies. The pro-inflammatory immune response mounted against malaria down-regulates iron absorption in the gut, making provision of oral iron supplements during malarial infection of questionable utility. The present study proposes to use iron stable isotopes and a randomized design to test whether starting 4 weeks of iron therapy immediately after antimalarial treatment or 4 weeks later is associated with greater iron incorporation into red blood cells at the time of initial administration of iron therapy and improved long-term hematological recovery. One hundred severely anemic (hemoglobin 5-9.9 g/dL) Ugandan children 6-59 mos with clinical signs of malaria who present to the Pediatric Acute Care Ward of Mulago Hospital in Kampala, Uganda, will be randomized to start iron immediately after antimalarial treatment on Day 0 (immediate group) or 4 weeks later on Day 28 (delayed group). Children will be assessed at the hospital on Day 0, Day 28 and Day 56 and will receive bi-weekly home visits for the 56-day study duration. The specific aims and corresponding hypotheses of the proposed study are:
Aim 1: Identify the sequencing of antimalarial treatment and iron therapy that results in the greatest red cell iron incorporation at the time of initial iron supplement administration. The working hypothesis is that red cell iron incorporation will be greater at the time of initial supplement administration in children starting iron 4 weeks after antimalarial treatment (delayed group) compared to children starting iron concurrently with antimalarial treatment (immediate group), due to more complete parasite clearance and resolution of inflammation, permitting better iron uptake, distribution, and utilization.
Aim 2: Determine whether long-term hematological recovery is impacted by immediate vs. delayed iron. The working hypothesis is that delayed iron treatment will be associated with greater hemoglobin and improved iron status at Day 56 compared to immediate treatment due to more complete parasite clearance and consequent improved iron absorption and use in the delayed group.
The results of this study will establish a physiologically-based framework for the optimal timing of antimalarial treatment and iron therapy upon which future interventions aimed at improving iron status in malaria-endemic regions can be built, thus helping to reduce the morbidity and mortality and ensure the full neurobehavioral development of the millions of severely anemic children suffering from iron-deficiency and malaria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immediate iron | Experimental | Dietary Supplement: Immediate ironChildren who start 4 weeks of iron therapy on Day 0 |
| Delayed iron | Experimental | Dietary Supplement: Delayed ironChildren who start 4 weeks of iron therapy on Day 28 |
Who may qualify
- Ages
- 6 to 59 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 6 - 59 months of age
- Hemoglobin 5.0 - 9.9 g/dL according to HemoCue
- Temperature > 37.5°C or history of fever in past 24 hours
- P. falciparum on blood smear at Acute Care Unit
- Residence<50 km of study hospital
Key exclusion criteria (3 listed)
- Impaired consciousness on physical exam or history of coma with present illness
- Seizure activity prior to or during admission
- Known sickle cell disease 4) Acute malnutrition
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 |
|---|---|---|
| Immediate ironAlso: Ferrous sulfate syrupChildren who start 4 weeks of iron therapy on Day 0 | Dietary supplement | Immediate iron |
| Delayed ironChildren who start 4 weeks of iron therapy on Day 28 | Dietary supplement | Delayed iron |
Primary outcome
Percent red blood cell iron incorporation on Day 0 in children in the immediate group vs. percent red blood cell iron incorporation on Day 28 in children in the delayed group
Time frame: 56 days
All children will receive iron stable isotope 57Fe on Day 0 and iron stable isotope 58Fe on Day 28. Children in the immediate group will begin 27 days of daily iron syrup at home on Day 1. Children in the delayed group will begin 27 days of daily iron syrup at home on Day 29. All children will be assessed at the hospital at Day 28 and Day 56.
1 secondary outcome
Hematological recovery in the immediate vs. delayed groups on Day 56
Time frame: 56 days
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 30 Nov 2015.
- Derived from this study: PubMed 27358418Cusick SE, Opoka RO, Abrams SA, John CC, Georgieff MK, Mupere E. Delaying Iron Therapy until 28 Days after Antimalarial Treatment Is Associated with Greater Iron Incorporation and Equivalent Hematologic Recovery after 56 Days in Children: A Randomized Controlled Trial. J Nutr. 2016 Sep;146(9):1769-74. doi: 10.3945/jn.116.233239. Epub 2016 Jun 29.
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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.
Sarah Cusick, Ph.D. principal investigator
University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immediate iron and Delayed iron in people with Iron Deficiency and Malaria, run by University of Minnesota at 1 site in Uganda.
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 5 inclusion and 3 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 30 Nov 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 Uganda. 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?
Percent red blood cell iron incorporation on Day 0 in children in the immediate group vs. percent red blood cell iron incorporation on Day 28 in children in the delayed group (time frame: 56 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01754701, which also lists 1 linked publication.
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 30 Nov 2015.