- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03617575
The Effect of Lactoferrin and Dosing Regimen on Iron Absorption From a Maize-based Porridge in Kenyan Infants
The Effect of Apo- and Holo-Lactoferrin and Dosing Regimen on Iron Absorption From a Maize-based Porridge in Kenyan Infants
Study Overview
Status
Conditions
Detailed Description
Infants and young children in sub-Saharan Africa have high rates of iron deficiency anemia (IDA), which adversely affects their growth and cognitive development. In-home iron fortification of complementary foods using micronutrient powders (MNPs) reduces risk for IDA by ensuring that the iron needs of infants and young children are met without changing their traditional diet. Oral iron syrups, typically containing iron as ferrous sulfate, can also be given to prevent/correct IDA. However, iron absorption from MNPs and iron syrups, particularly when given with complementary foods high in inhibitors of iron absorption, is low. Thus, there is a need to find iron formulations with higher bioavailability for use in African infants. In a recent trial in Kenya, the investigators demonstrated that a prebiotic could improve iron bioavailability from an iron-containing MNP.
In this study, the investigators plan to assess the human milk compound lactoferrin (Lf) as a possible enhancer of iron absorption. Lf is an important iron-binding protein in human milk, which has been thought to be responsible for the high bioavailability of breast-milk iron. It has many biological functions, including iron absorption, antimicrobial activity, immunomodulatory effects and stimulatory effect on cell proliferation. Lf has different iron binding statuses: the iron free form (apo-Lf) and the iron-saturated form (holo-Lf). One of the two main biological activities of Lf provided by the diet is the control of iron uptake, which is mediated by the Lf receptor (LFR) as undigested Lf can bind to LFR and facilitate the uptake of iron. Therefore, Lf may be a nutritional iron source and may enhance iron absorption in infants. To evaluate the possible role of Lf on the availability of iron, iron absorption will be measured from bovine Lf (bLf). BLf has GRAS (generally considered as safe) status by the US Food and Drug Administration.
To optimize iron absorption, timing of supplementation might as well be important. Hepcidin, a key regulator of systemic iron balance and a single dose of iron can increase hepcidin levels and potentially inhibit iron absorption from a second dose, consumed close in time to the first dose. The investigators will conduct two studies, where 24 infants aged 3-14 months in Msambweni, Kenya, will be enrolled. In study 1, on three alternate mornings, these infants will consume maize porridge containing a low iron dose (1.5 mg) to compare iron absorption between meals with apo-Lf, holo-Lf and ferrous sulfate (FeSO4) as a reference; and whether the addition of either apo- or holo-Lf has a beneficial effect on iron absorption. The investigators hypothesize that iron absorption will be higher when holo-Lf is present in the meal compared to apo-Lf. In study 2, the investigators want to compare two different dosing regimens, in which they measure iron absorption after one-day washout period and after a two-day washout period, and hypothesize that absorption will be higher after 2 days of washout.
The data from this project will provide valuable information towards the development of new, highly bioavailable iron formulations and dosing regimen that is most efficient.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Kwale County
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Msambweni, Kwale County, Kenya
- Msambweni County Referral Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age of 3-14 months at baseline
- Complementary feeding of the infant has already started
- Assessment of good health as assessed by professional staff at Msambweni District Hospital
- The caregiver is willing to participate in the study
- The informed consent form has been read and signed by the caregiver (or has been read out to the caregiver in case of illiteracy)
- Willingness of the caregiver to provide five blood samples from their child in total during the studies during the visits at the hospital
- Residence in the study for the period of the study
Exclusion Criteria:
- Hb <70 g/L
- Severe underweight (waz <-3)
- Severe wasting (whz <-3)
- Chronic or acute illness or other conditions that in the opinion of the principle investigator or co-researchers would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol
- Participants taking part in other studies requiring the drawing of blood
- Regular intake (>2 days) of iron-containing mineral and vitamin supplements or fortified foods within the last 2 months
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: apo-Lactoferrin
unsaturated (= no iron) form of Lactoferrin Lactoferrin is a bovine milk protein Test Meal A1
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1.41 g of apo-Lactoferrin will be given together with 1.42 mg FeSO4 (0.08 mg of iron naturally in apo-Lf [total of 1.5 mg iron]) in a maize porridge (extrinsically labeled)
|
Placebo Comparator: holo-Lactoferrin
saturated (= contains a certain amount of iron) form of Lactoferrin Lactoferrin is a bovine milk protein Test Meal B1
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1.41 g of holo-Lactoferrin (intrinsically labeled with 1.5 mg 57Fe) will be given together in a maize porridge
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Placebo Comparator: FeSO4
Ferrous sulfate = FeSO4 acting as the reference Test Meal C1
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1.5 mg FeSO4 as 54Fe in a maize porridge
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Placebo Comparator: 1. FeSO4
Ferrous sulfate = FeSO4 Test Meal A2
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10 mg 56Fe + 2 mg 54Fe Is the 1.
FeSO4 meal in maize porridge
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Placebo Comparator: FeSO4 after 1 day break
Ferrous sulfate = FeSO4 Test Meal B2
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10 mg 56Fe + 2 mg 57Fe Is the 2. FeSO4 in maize porridge with a 1 day washout period
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Placebo Comparator: FeSO4 after 2 day break
Ferrous sulfate = FeSO4 Test Meal C2
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10 mg 56Fe + 2 mg 58Fe Is the 3. FeSO4 in maize porridge with a 2 day washout period
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fractional iron absorption (%)
Time Frame: Day 21
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Fractional iron absorption from 3 different test meals (apo-, holo-Lactoferrin and FeSO4) erythrocyte incorporation of stable iron isotopes into red blood cells 14 days after test meal
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Day 21
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Fractional iron absorption (%)
Time Frame: Day 41
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Fractional iron absorption after 2 different washout periods after receiving test meals (1 day vs 2 days)
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Day 41
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Hemoglobin in g/dL (in blood)
Time Frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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to identify anemia
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Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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Plasma ferritin in µg/L (in blood)
Time Frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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to identify iron deficiency
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Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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Soluble transferrin receptor in mg/L (in blood)
Time Frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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to identify iron deficiency
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Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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C-reactive protein in mg/L (in blood)
Time Frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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to identify acute inflammation, which inhibits iron absorption
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Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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alpha-1-glycoprotein in g/L (in blood)
Time Frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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to identify chronic inflammation, which inhibits iron absorption
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Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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Plasma hepcidin (in blood)
Time Frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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one of major iron absorption regulators
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Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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Collaborators and Investigators
Publications and helpful links
General Publications
- Mikulic N, Uyoga MA, Mwasi E, Stoffel NU, Zeder C, Karanja S, Zimmermann MB. Iron Absorption is Greater from Apo-Lactoferrin and is Similar Between Holo-Lactoferrin and Ferrous Sulfate: Stable Iron Isotope Studies in Kenyan Infants. J Nutr. 2020 Dec 10;150(12):3200-3207. doi: 10.1093/jn/nxaa226.
- Uyoga MA, Mikulic N, Paganini D, Mwasi E, Stoffel NU, Zeder C, Karanja S, Zimmermann MB. The effect of iron dosing schedules on plasma hepcidin and iron absorption in Kenyan infants. Am J Clin Nutr. 2020 Oct 1;112(4):1132-1141. doi: 10.1093/ajcn/nqaa174.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Hematologic Diseases
- Anemia, Hypochromic
- Anemia
- Iron Metabolism Disorders
- Anemia, Iron-Deficiency
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Urological Agents
- Lactoferrin
- Fesoterodine
Other Study ID Numbers
- Fe_LF
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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