Iron-deficiencyNCT03617575
The Effect of Lactoferrin and Dosing Regimen on Iron Absorption From a Maize-based Porridge in Kenyan Infants
A study testing apo-Lactoferrin, holo-Lactoferrin and FeSO4 in people with Iron-deficiency, run by Swiss Federal Institute of Technology at 1 site in Kenya.
Trial summary
The purpose of this study is to measure iron absorption from maize-based porridge fortified with either apo-lactoferrin, holo-lactoferrin or ferrous sulfate and to test whether there is an effect of these. Read more about this study
- Who is it for?
- Ages 3 to 14 monthsHealthy volunteers can take part
- Conditions the study is for
- Iron-deficiency
- What is being tested?
- apo-Lactoferrin, holo-Lactoferrin and FeSO4
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteKenya
- Study dates
- 11 Dec 2018to 30 Mar 2019
- 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 3 to 14 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Apo- and Holo-Lactoferrin and Dosing Regimen on Iron Absorption From a Maize-based Porridge in Kenyan Infants
The purpose of this study is to measure iron absorption from maize-based porridge fortified with either apo-lactoferrin, holo-lactoferrin or ferrous sulfate and to test whether there is an effect of these. Additionally, iron absorption from maize-based porridge containing 12 mg ferrous sulfate will be measured when consumed every other day versus every third day.
Read the 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.
- Conditions
- Iron-deficiency
- Being tested
- apo-Lactoferrin, holo-Lactoferrin, FeSO4, 1. FeSO4, FeSO4 after 1 day break
- Medical subject headings
- Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
apo-LactoferrinDietary supplement
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)
holo-LactoferrinDietary supplement
1.41 g of holo-Lactoferrin (intrinsically labeled with 1.5 mg 57Fe) will be given together in a maize porridge
FeSO4Dietary supplement
1.5 mg FeSO4 as 54Fe in a maize porridge
1. FeSO4Dietary supplement
10 mg 56Fe + 2 mg 54Fe Is the 1. FeSO4 meal in maize porridge
FeSO4 after 1 day breakDietary supplement
10 mg 56Fe + 2 mg 57Fe Is the 2. FeSO4 in maize porridge with a 1 day washout period
FeSO4 after 2 day breakDietary supplement
10 mg 56Fe + 2 mg 58Fe Is the 3. FeSO4 in maize porridge with a 2 day washout period
| Study group | Role | What they receive |
|---|---|---|
| apo-Lactoferrin | Placebo comparator | unsaturated (= no iron) form of Lactoferrin Lactoferrin is a bovine milk protein Test Meal A1 Receives: Dietary Supplement: apo-Lactoferrin |
| holo-Lactoferrin | Placebo comparator | saturated (= contains a certain amount of iron) form of Lactoferrin Lactoferrin is a bovine milk protein Test Meal B1 Receives: Dietary Supplement: holo-Lactoferrin |
| FeSO4 | Placebo comparator | Ferrous sulfate = FeSO4 acting as the reference Test Meal C1 Receives: Dietary Supplement: FeSO4 |
| 1. FeSO4 | Placebo comparator | Ferrous sulfate = FeSO4 Test Meal A2 Receives: Dietary Supplement: 1. FeSO4 |
| FeSO4 after 1 day break | Placebo comparator | Ferrous sulfate = FeSO4 Test Meal B2 Receives: Dietary Supplement: FeSO4 after 1 day break |
| FeSO4 after 2 day break | Placebo comparator | Ferrous sulfate = FeSO4 Test Meal C2 Receives: Dietary Supplement: FeSO4 after 2 day break |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fractional iron absorption (%)
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
Measured: Day 21
Secondary outcomes (7)
Fractional iron absorption (%)
Fractional iron absorption after 2 different washout periods after receiving test meals (1 day vs 2 days)
Measured: Day 41
Hemoglobin in g/dL (in blood)
to identify anemia
Measured: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
Plasma ferritin in µg/L (in blood)
to identify iron deficiency
Measured: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
Soluble transferrin receptor in mg/L (in blood)
to identify iron deficiency
Measured: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
C-reactive protein in mg/L (in blood)
to identify acute inflammation, which inhibits iron absorption
Measured: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
alpha-1-glycoprotein in g/L (in blood)
to identify chronic inflammation, which inhibits iron absorption
Measured: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
Plasma hepcidin (in blood)
one of major iron absorption regulators
Measured: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start11 Dec 2018
- Primary completion30 Mar 2019
- Study completion30 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Iron-deficiencyStudies of the same condition, open and under way.
- 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
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Federal Institute of Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Michael B. Zimmermann, Swiss Federal Institute of Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03617575
- Sponsor's protocol ID
- Fe_LF
- Status last verified
- May 2020
- First submitted
- 24 Jul 2018
- Last updated
- 13 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32886113Uyoga 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.
PubMed 32678434
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Apo- and Holo-Lactoferrin and Dosing Regimen on Iron Absorption From a Maize-based Porridge in Kenyan Infants
- ClinicalTrials.gov ID
- NCT03617575
- Acronym / sponsor ID
- Fe_LF
- Conditions
- Iron-deficiency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Swiss Federal Institute of TechnologyUniversity, hospital or other
- Study start
- 11 Dec 2018 (actual)
- Primary completion
- 30 Mar 2019 (actual)
- Study completion
- 30 Mar 2019 (actual)
- First posted
- 6 Aug 2018 (actual)
- 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 measure iron absorption from maize-based porridge fortified with either apo-lactoferrin, holo-lactoferrin or ferrous sulfate and to test whether there is an effect of these. Additionally, iron absorption from maize-based porridge containing 12 mg ferrous sulfate will be measured when consumed every other day versus every third day.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| apo-Lactoferrin | Placebo comparator | Dietary Supplement: apo-Lactoferrinunsaturated (= no iron) form of Lactoferrin Lactoferrin is a bovine milk protein Test Meal A1 |
| holo-Lactoferrin | Placebo comparator | Dietary Supplement: holo-Lactoferrinsaturated (= contains a certain amount of iron) form of Lactoferrin Lactoferrin is a bovine milk protein Test Meal B1 |
| FeSO4 | Placebo comparator | Dietary Supplement: FeSO4Ferrous sulfate = FeSO4 acting as the reference Test Meal C1 |
| 1. FeSO4 | Placebo comparator | Dietary Supplement: 1. FeSO4Ferrous sulfate = FeSO4 Test Meal A2 |
| FeSO4 after 1 day break | Placebo comparator | Dietary Supplement: FeSO4 after 1 day breakFerrous sulfate = FeSO4 Test Meal B2 |
| FeSO4 after 2 day break | Placebo comparator | Dietary Supplement: FeSO4 after 2 day breakFerrous sulfate = FeSO4 Test Meal C2 |
Who may qualify
- Ages
- 3 to 14 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
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 |
|---|---|---|
| apo-Lactoferrin1.41 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) | Dietary supplement | apo-Lactoferrin |
| holo-Lactoferrin1.41 g of holo-Lactoferrin (intrinsically labeled with 1.5 mg 57Fe) will be given together in a maize porridge | Dietary supplement | holo-Lactoferrin |
| FeSO41.5 mg FeSO4 as 54Fe in a maize porridge | Dietary supplement | FeSO4 |
| 1. FeSO410 mg 56Fe + 2 mg 54Fe Is the 1. FeSO4 meal in maize porridge | Dietary supplement | 1. FeSO4 |
| FeSO4 after 1 day break10 mg 56Fe + 2 mg 57Fe Is the 2. FeSO4 in maize porridge with a 1 day washout period | Dietary supplement | FeSO4 after 1 day break |
| FeSO4 after 2 day break10 mg 56Fe + 2 mg 58Fe Is the 3. FeSO4 in maize porridge with a 2 day washout period | Dietary supplement | FeSO4 after 2 day break |
Primary outcome
Fractional iron absorption (%)
Time frame: Day 21
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
7 secondary outcomes
Fractional iron absorption (%)
Time frame: Day 41
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
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
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
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
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
Plasma hepcidin (in blood)
Time frame: Baseline, Day 21, Day 24 (after 1 day washout), Day 27 (after 2 days washout), Day 41
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 13 May 2020.
- Derived from this study: PubMed 32886113Mikulic 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.
- Derived from this study: PubMed 32678434Uyoga 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.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing apo-Lactoferrin, holo-Lactoferrin and FeSO4 in people with Iron-deficiency, run by Swiss Federal Institute of Technology at 1 site in Kenya.
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 7 inclusion and 6 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 13 May 2020. 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 Kenya. 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. Some participants in this study may receive a placebo. 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?
Fractional iron absorption (%) (time frame: Day 21). 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 NCT03617575, which also lists 2 linked publications.
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 13 May 2020.