Iron Deficiency AnemiaNCT04721964
Evaluation of the Effects of Routine Iron Supplementation in Children on Gastrointestinal Iron Losses
A study testing Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India) in people with Iron Deficiency Anemia and Gastro Intestinal Bleeding, run by Swiss Federal Institute of Technology at 1 site in Kenya.
Trial summary
Iron deficiency anaemia (IDA) is common among infants and young children in sub-Saharan Africa.Oral iron administration is usually recom-mended as cost effective measure to prevent and treat iron deficiency (ID) and IDA during childhood. Read more about this study
- Who is it for?
- Ages 23 to 29 monthsHealthy volunteers can take part
- Conditions the study is for
- Iron Deficiency Anemia, Gastro Intestinal Bleeding, Iron-deficiency
- What is being tested?
- Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteKenya
- Study dates
- 25 Feb 2021to 16 Jun 2021
- 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 23 to 29 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Participation in former Fe_HMO_GOS study (JKUAT/IERC No. 301019) or INSPIRE study (JKUAT/IERC No. JKU/2/4/896B).
- Mildly to moderately anaemic defined as 9.0 g/dL ≤ Hb < 11 g/dL.
- Iron deficiency defined as ZPP >80μmol/mol.
- Willingness of the caregiver to participate in the study.
- Residence in the study area for the period of the study.
- The informed consent form has been read and signed by the participant's caregiver (or has been read out to the participant's caregiver in case of illiteracy)
- Assessment of good health by professional staff at Msambweni District Hospital.
Who cannot join
- Hb <9 g/L or >11 g/L.
- Zinc ProtoPorphyrin ≤80 μmol/mol.
- Severe underweight (Z-score weight-for-age ≤-3).
- Severe wasting (Z-score weight-for-height ≤-3).
- Antibiotics consumption in the 7 days prior to screening.
- Consumption of iron supplements in the 14 days prior to screening.
- Any severe metabolic, gastrointestinal, kidney or chronic disease such as diabetes, hepatitis, hypertension, cancer or cardiovascular diseases (according to the guardian's statement or medical examination (health booklet)).
- Participants taking part in other studies requiring the drawing of blood or involving medical or physical interventions.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Effects of Routine Iron Supplementation in Children on Gastrointestinal Iron Losses.
Iron deficiency anaemia (IDA) is common among infants and young children in sub-Saharan Africa.Oral iron administration is usually recom-mended as cost effective measure to prevent and treat iron deficiency (ID) and IDA during childhood. In Kenya, national nutrition policies for anaemia prevention recommend a daily dose of 3-6 mg ele-mental iron per kg body weight if a child is diagnosed with anaemia.
Using a novel technology, recent research found increased iron losses during iron supplementation. In an explorative analysis of stool samples collected from Gambian toddlers (Speich et al., 2020), an increase in faecal iron losses during iron supplementation was reported. The present study is aiming to analyse a relationship between routine iron supplementation and increased faecal occult blood losses in 24 Kenyan children with anaemia and iron deficiency in a more structured manner.
Secondary objectives of the study are to measure and monitor iron and inflammatory status during the course of the study and to quantify long-term iron absorption and iron losses during a 12-weeks iron supplementation period, in order to put iron balance into relationship to occurring faecal occult blood losses during such an intervention.
Read the detailed description
Infants and young children in sub-Saharan Africa have high rates of iron deficiency anaemia (IDA), which adversely affects their growth and cognitive development. WHO recommends daily administration of 3 mg elemental iron per kg body weight in form of drops or syrup in 6-23 month-old ID or anaemic infants. In settings where anaemia prevalence in this age group is >40%, WHO further recommends daily administration of 10-12.5 mg elemental iron for prevention of ID and anaemia. The Kenyan Ministry of Health adopted the WHO strategy to treat IDA in its "Basic Paediatric Protocols" released in 2016, and specified a dose of 3-6 mg elemental Fe per kg body weight and day.
WHO guidelines for anaemia prevention and control in infants aged 6-23 months are based on a systematic review and meta-analysis of randomized controlled trials investigating the effect of daily iron supplementation on health in infants. The review reported a significantly lower risk of iron-deficiency anaemia in infants when supplemented. However, iron supplements and iron-containing micronutrient powders (MNPs) do not always show efficacy; for example, in a recent large intervention trial in Pakistan, there was no significant effect of 12 months of iron supplementation on haemoglobin status.
Among the many potential factors contributing to the limited success of health and nutrition policies in reducing the prevalence of iron deficiency, increased iron losses during iron supplementation have not been considered. In a recent study in Gambian toddlers, a 3.4-fold increase in iron losses was detected, specifically from 0.22 (0.19;0.29) mg/d to 0.75 (0.55;0.87) mg/d, during a 12-week iron intervention with daily consumption of 12 mg iron as ferrous fumarate in MNPs routinely distributed by the United Nations Children's Fund and the World Food Program. Furthermore, the administered iron dose significantly correlated with faecal haemoglobin concentration in the Gambian toddlers. In a recent iron supplementation pilot study in Kenyan toddlers, the investigators measured a significant increase in faecal haemoglobin concentration during iron supplementation. Increased basal iron losses during iron supplementation could also be detected in 10 Swiss women. Several endoscopy studies have suggested iron supplementation may cause irritation/inflammation of the gut mucosa, potentially leading to gastrointestinal blood losses.
To explore a potential relationship between iron supplementation with common iron supplements and increased faecal occult (small traces of blood, not visible in stool) blood losses, this study will measure haemoglobin and porphyrin content in stool samples collected before and throughout a 91-day iron supplementation intervention. Intervention product will be 6 mg iron / kg body weight as ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India) administered daily. Faecal occult blood losses will also be compared to absolute iron losses determined by the recently developed dilution of stable iron isotopes methodology. The study population will consist of 24 anaemic 2-years old children in Kwale County of southern coastal Kenya. The hypothesis of the investigators is that iron status will improve, but faecal occult blood losses will increase. The data from this project may provide valuable information towards the development of safer and more effective iron supplementation regimens.
- Being tested
- Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India)
- Medical subject headings
- Anemia, Iron-Deficiency, Gastrointestinal Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India)Dietary supplement
Daily supplementation with iron syrup for 13 weeks. The dosage will be calculated based on body weight and adjusted after 4 and 8 weeks of intervention
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | All 24 participants will daily consume 6 mg iron/kg body weight for 13 weeks to correct their anaemia and increase their iron stores. Receives: Dietary Supplement: Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fecal occult blood concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Measured: Day 4-7 (baseline)
Fecal occult blood concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Measured: Day 32-35
Fecal occult blood concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Measured: Day 60-63
Fecal occult blood concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Measured: Day 95-98
Secondary outcomes (40)
Iron status: Hemoglobin (g/dl) (Hb)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. Hb concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Baseline (day 7)
Iron status: Zinc protoporphyrin (µmol/mol) (ZPP)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. ZPP concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Baseline (day 7)
Iron status: Soluble Transferrin Receptor (mg/L) (sTfR)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of sTfR concentration.
Measured: Baseline (day 7)
Iron status: Serum Ferritin (ug/L) (SF)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of SF concentration.
Measured: Baseline (day 7)
Iron status: Serum Hepcidin (nM)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit.1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland, for analysis of serum hepcidin.
Measured: Baseline (day 7)
Iron status: Hemoglobin (g/dl)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. Hb concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Day 35
Iron status: Zinc protoporphyrin (µmol/mol)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. ZPP concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Day 35
Iron status: Soluble Transferrin Receptor (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of sTfR concentration.
Measured: Day 35
Iron status: Serum Ferritin (ug/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of SF concentration.
Measured: Day 35
Iron status: Serum Hepcidin (nM)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit.1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland, for analysis of serum hepcidin.
Measured: Day 35
Iron status: Hemoglobin (g/dl)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. Hb concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Day 63
Iron status: Zinc protoporphyrin (µmol/mol)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. ZPP concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Day 63
Iron status: Soluble Transferrin Receptor (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of sTfR concentration.
Measured: Day 63
Iron status: Serum Ferritin (ug/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of SF concentration.
Measured: Day 63
Iron status: Serum Hepcidin (nM)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit.1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland, for analysis of serum hepcidin.
Measured: Day 63
Iron status: Hemoglobin (g/dl)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. Hb concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Day 98
Iron status: Zinc protoporphyrin (µmol/mol)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. ZPP concentration will be measured immediately after blood withdrawal using an iCheck Anaemia diagnostic device (BioAnalyt GmbH, Teltow, Germany).
Measured: Day 98
Iron status: Soluble Transferrin Receptor (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of sTfR concentration.
Measured: Day 98
Iron status: Serum Ferritin (ug/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quatification of SF concentration.
Measured: Day 98
Iron status: Serum Hepcidin (nM)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit.1 mL full blood samples will then be aliquoted and the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland, for analysis of serum hepcidin.
Measured: Day 98
Inflammation status: alpha Glycoprotein (g/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of AGP.
Measured: Baseline (day 7)
Inflammation status: C-reactive protein (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of CRP.
Measured: Baseline (day 7)
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland.
I-FABP concentrations will be analysed after completion of the study at the ETH laboratory, using commercially available ELISA kits.
Measured: Baseline (day 7)
Inflammation status: C-reactive protein (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of CRP.
Measured: Day 35
Inflammation status: alpha Glycoprotein (g/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of AGP.
Measured: Day 35
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland.
I-FABP concentrations will be analysed after completion of the study at the ETH laboratory, using commercially available ELISA kits.
Measured: Day 35
Inflammation status: C-reactive protein (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of CRP.
Measured: Day 63
Inflammation status: alpha Glycoprotein (g/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of AGP.
Measured: Day 63
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland.
I-FABP concentrations will be analysed after completion of the study at the ETH laboratory, using commercially available ELISA kits.
Measured: Day 63
Inflammation status: C-reactive protein (mg/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of CRP. .
Measured: Day 98
Inflammation status: alpha Glycoprotein (g/L)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. A serum aliquot of only 100-200 μL will be analysed externally in the VitMin Lab, Willstaett, Germany, using a multiplex ELISA assay developed by Erhardt et al. (Erhardt et al., 2004) for quantification of AGP.
Measured: Day 98
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. After aliquotting 1 mL full blood samples, the remaining blood samples will be centrifuged, all serum aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland.
I-FABP concentrations will be analysed after completion of the study at the ETH laboratory, using commercially available ELISA kits.
Measured: Day 98
Red Blood Cells isotopic composition
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will be aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. For iron isotopic composition each blood sample will be analysed in duplicate under chemical blank monitoring. Whole blood samples will be mineralised using an HNO3 and microwave digestion. This is followed by a separation of the sample matrix by anion-exchange chromatography and a subsequent precipitation step with ammonium hydroxide. The isotopic analyses will be performed by inductively coupled plasma mass spectrometry (ICPMS) using a high resolution double focusing mass spectrometer equipped with a multi-collector system for simultaneous ion beam detection.
Measured: Baseline (day 7)
Red Blood Cells isotopic composition
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will be aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. For iron isotopic composition each blood sample will be analysed in duplicate under chemical blank monitoring. Whole blood samples will be mineralised using an HNO3 and microwave digestion. This is followed by a separation of the sample matrix by anion-exchange chromatography and a subsequent precipitation step with ammonium hydroxide. The isotopic analyses will be performed by inductively coupled plasma mass spectrometry (ICPMS) using a high resolution double focusing mass spectrometer equipped with a multi-collector system for simultaneous ion beam detection.
Measured: Day 35
Red Blood Cells isotopic composition
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will be aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. For iron isotopic composition each blood sample will be analysed in duplicate under chemical blank monitoring. Whole blood samples will be mineralised using an HNO3 and microwave digestion. This is followed by a separation of the sample matrix by anion-exchange chromatography and a subsequent precipitation step with ammonium hydroxide. The isotopic analyses will be performed by inductively coupled plasma mass spectrometry (ICPMS) using a high resolution double focusing mass spectrometer equipped with a multi-collector system for simultaneous ion beam detection.
Measured: Day 63
Red Blood Cells isotopic composition
Venipuncture blood withdrawal (3 mL) will be performed at each hospital visit. 1 mL full blood samples will be aliquoted and stored at -20°C at the study site until all samples will be shipped frozen to ETH Zurich, Switzerland. For iron isotopic composition each blood sample will be analysed in duplicate under chemical blank monitoring. Whole blood samples will be mineralised using an HNO3 and microwave digestion. This is followed by a separation of the sample matrix by anion-exchange chromatography and a subsequent precipitation step with ammonium hydroxide. The isotopic analyses will be performed by inductively coupled plasma mass spectrometry (ICPMS) using a high resolution double focusing mass spectrometer equipped with a multi-collector system for simultaneous ion beam detection.
Measured: Day 98
Fecal calprotectin concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Stool aliquots will be shipped frozen to ETH Zurich, Switzerland, for determination of calprotectin content using commercially available calprotectin kits.
Measured: Day 4-7 (baseline)
Fecal calprotectin concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Stool aliquots will be shipped frozen to ETH Zurich, Switzerland, for determination of calprotectin content using commercially available calprotectin kits.
Measured: Day 32-35
Fecal calprotectin concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Stool aliquots will be shipped frozen to ETH Zurich, Switzerland, for determination of calprotectin content using commercially available calprotectin kits.
Measured: Day 60-63
Fecal calprotectin concentration
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Stool aliquots will be shipped frozen to ETH Zurich, Switzerland, for determination of calprotectin content using commercially available calprotectin kits.
Measured: Day 95-98
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2021
- Study start25 Feb 2021
- Primary completion16 Jun 2021
- Study completion16 Jun 2021
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 Deficiency AnemiaStudies 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective intervention study
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Swiss Federal Institute of Technology
- Sponsor type
- University, hospital or other
- Collaborators
- Jomo Kenyatta University of Agriculture and Technology
- Responsible party
- Principal investigator, Nicole Stoffel, Swiss Federal Institute of Technology
- Investigators
- Nicole U Stoffel, PhD, Principal investigator, ETH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04721964
- Sponsor's protocol ID
- FeLo
- Status last verified
- Jul 2021
- First submitted
- 13 Jan 2021
- Last updated
- 27 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Speich C, Wegmuller R, Brittenham GM, Zeder C, Cercamondi CI, Buhl D, Prentice AM, Zimmermann MB, Moretti D. Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe). Br J Haematol. 2021 Jan;192(1):179-189. doi: 10.1111/bjh.17039. Epub 2020 Aug 30.
PubMed 32862453Giorgetti A, Nyilima S, Stoffel NU, Moretti D, Mwasi E, Karanja S, Zeder C, Speich C, Netland C, Jin Z, Zimmermann MB, Brittenham GM. Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost. Br J Haematol. 2024 May;204(5):2057-2065. doi: 10.1111/bjh.19319. Epub 2024 Feb 1.
PubMed 38302093
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effects of Routine Iron Supplementation in Children on Gastrointestinal Iron Losses.
- ClinicalTrials.gov ID
- NCT04721964
- Acronym / sponsor ID
- FeLo
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Swiss Federal Institute of TechnologyUniversity, hospital or other
- Collaborators
- Jomo Kenyatta University of Agriculture and Technology
- Study start
- 25 Feb 2021 (actual)
- Primary completion
- 16 Jun 2021 (actual)
- Study completion
- 16 Jun 2021 (actual)
- First posted
- 25 Jan 2021 (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.
Iron deficiency anaemia (IDA) is common among infants and young children in sub-Saharan Africa.Oral iron administration is usually recom-mended as cost effective measure to prevent and treat iron deficiency (ID) and IDA during childhood. In Kenya, national nutrition policies for anaemia prevention recommend a daily dose of 3-6 mg ele-mental iron per kg body weight if a child is diagnosed with anaemia.
Using a novel technology, recent research found increased iron losses during iron supplementation. In an explorative analysis of stool samples collected from Gambian toddlers (Speich et al., 2020), an increase in faecal iron losses during iron supplementation was reported. The present study is aiming to analyse a relationship between routine iron supplementation and increased faecal occult blood losses in 24 Kenyan children with anaemia and iron deficiency in a more structured manner.
Secondary objectives of the study are to measure and monitor iron and inflammatory status during the course of the study and to quantify long-term iron absorption and iron losses during a 12-weeks iron supplementation period, in order to put iron balance into relationship to occurring faecal occult blood losses during such an intervention.
Detailed description
Infants and young children in sub-Saharan Africa have high rates of iron deficiency anaemia (IDA), which adversely affects their growth and cognitive development. WHO recommends daily administration of 3 mg elemental iron per kg body weight in form of drops or syrup in 6-23 month-old ID or anaemic infants. In settings where anaemia prevalence in this age group is >40%, WHO further recommends daily administration of 10-12.5 mg elemental iron for prevention of ID and anaemia. The Kenyan Ministry of Health adopted the WHO strategy to treat IDA in its "Basic Paediatric Protocols" released in 2016, and specified a dose of 3-6 mg elemental Fe per kg body weight and day.
WHO guidelines for anaemia prevention and control in infants aged 6-23 months are based on a systematic review and meta-analysis of randomized controlled trials investigating the effect of daily iron supplementation on health in infants. The review reported a significantly lower risk of iron-deficiency anaemia in infants when supplemented. However, iron supplements and iron-containing micronutrient powders (MNPs) do not always show efficacy; for example, in a recent large intervention trial in Pakistan, there was no significant effect of 12 months of iron supplementation on haemoglobin status.
Among the many potential factors contributing to the limited success of health and nutrition policies in reducing the prevalence of iron deficiency, increased iron losses during iron supplementation have not been considered. In a recent study in Gambian toddlers, a 3.4-fold increase in iron losses was detected, specifically from 0.22 (0.19;0.29) mg/d to 0.75 (0.55;0.87) mg/d, during a 12-week iron intervention with daily consumption of 12 mg iron as ferrous fumarate in MNPs routinely distributed by the United Nations Children's Fund and the World Food Program. Furthermore, the administered iron dose significantly correlated with faecal haemoglobin concentration in the Gambian toddlers. In a recent iron supplementation pilot study in Kenyan toddlers, the investigators measured a significant increase in faecal haemoglobin concentration during iron supplementation. Increased basal iron losses during iron supplementation could also be detected in 10 Swiss women. Several endoscopy studies have suggested iron supplementation may cause irritation/inflammation of the gut mucosa, potentially leading to gastrointestinal blood losses.
To explore a potential relationship between iron supplementation with common iron supplements and increased faecal occult (small traces of blood, not visible in stool) blood losses, this study will measure haemoglobin and porphyrin content in stool samples collected before and throughout a 91-day iron supplementation intervention. Intervention product will be 6 mg iron / kg body weight as ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India) administered daily. Faecal occult blood losses will also be compared to absolute iron losses determined by the recently developed dilution of stable iron isotopes methodology. The study population will consist of 24 anaemic 2-years old children in Kwale County of southern coastal Kenya. The hypothesis of the investigators is that iron status will improve, but faecal occult blood losses will increase. The data from this project may provide valuable information towards the development of safer and more effective iron supplementation regimens.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective intervention study
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Dietary Supplement: Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India)All 24 participants will daily consume 6 mg iron/kg body weight for 13 weeks to correct their anaemia and increase their iron stores. |
Who may qualify
- Ages
- 23 to 29 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Participation in former Fe_HMO_GOS study (JKUAT/IERC No. 301019) or INSPIRE study (JKUAT/IERC No. JKU/2/4/896B).
- Mildly to moderately anaemic defined as 9.0 g/dL ≤ Hb < 11 g/dL.
- Iron deficiency defined as ZPP >80μmol/mol.
- Willingness of the caregiver to participate in the study.
- Residence in the study area for the period of the study.
Key exclusion criteria (8 listed)
- Hb <9 g/L or >11 g/L.
- Zinc ProtoPorphyrin ≤80 μmol/mol.
- Severe underweight (Z-score weight-for-age ≤-3).
- Severe wasting (Z-score weight-for-height ≤-3).
- Antibiotics consumption in the 7 days prior to screening.
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 |
|---|---|---|
| Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India)Daily supplementation with iron syrup for 13 weeks. The dosage will be calculated based on body weight and adjusted after 4 and 8 weeks of intervention | Dietary supplement | Intervention |
Primary outcome
Fecal occult blood concentration
Time frame: Day 4-7 (baseline)
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Fecal occult blood concentration
Time frame: Day 32-35
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Fecal occult blood concentration
Time frame: Day 60-63
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
Fecal occult blood concentration
Time frame: Day 95-98
72 h stool samples will be collected from the study participants during 4 collection periods (day 4-7 (baseline), day 32-35, day 60-63, day 95-98). Fecal occult blood concentration in the samples will be estimated from haemoglobin and porphyrin content in stool samples. These measurements will be assessed from stool aliquots, that will be shipped frozen to Mayo Clinic Laboratory (Rochester, USA), using highly specific hemoquant assay.
40 secondary outcomes
Iron status: Hemoglobin (g/dl) (Hb)
Time frame: Baseline (day 7)
Iron status: Zinc protoporphyrin (µmol/mol) (ZPP)
Time frame: Baseline (day 7)
Iron status: Soluble Transferrin Receptor (mg/L) (sTfR)
Time frame: Baseline (day 7)
Iron status: Serum Ferritin (ug/L) (SF)
Time frame: Baseline (day 7)
Iron status: Serum Hepcidin (nM)
Time frame: Baseline (day 7)
Iron status: Hemoglobin (g/dl)
Time frame: Day 35
Iron status: Zinc protoporphyrin (µmol/mol)
Time frame: Day 35
Iron status: Soluble Transferrin Receptor (mg/L)
Time frame: Day 35
Iron status: Serum Ferritin (ug/L)
Time frame: Day 35
Iron status: Serum Hepcidin (nM)
Time frame: Day 35
Iron status: Hemoglobin (g/dl)
Time frame: Day 63
Iron status: Zinc protoporphyrin (µmol/mol)
Time frame: Day 63
Iron status: Soluble Transferrin Receptor (mg/L)
Time frame: Day 63
Iron status: Serum Ferritin (ug/L)
Time frame: Day 63
Iron status: Serum Hepcidin (nM)
Time frame: Day 63
Iron status: Hemoglobin (g/dl)
Time frame: Day 98
Iron status: Zinc protoporphyrin (µmol/mol)
Time frame: Day 98
Iron status: Soluble Transferrin Receptor (mg/L)
Time frame: Day 98
Iron status: Serum Ferritin (ug/L)
Time frame: Day 98
Iron status: Serum Hepcidin (nM)
Time frame: Day 98
Inflammation status: alpha Glycoprotein (g/L)
Time frame: Baseline (day 7)
Inflammation status: C-reactive protein (mg/L)
Time frame: Baseline (day 7)
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Time frame: Baseline (day 7)
Inflammation status: C-reactive protein (mg/L)
Time frame: Day 35
Inflammation status: alpha Glycoprotein (g/L)
Time frame: Day 35
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Time frame: Day 35
Inflammation status: C-reactive protein (mg/L)
Time frame: Day 63
Inflammation status: alpha Glycoprotein (g/L)
Time frame: Day 63
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Time frame: Day 63
Inflammation status: C-reactive protein (mg/L)
Time frame: Day 98
Inflammation status: alpha Glycoprotein (g/L)
Time frame: Day 98
Inflammation status: Fatty Acids Binding Protein (ng/ml)
Time frame: Day 98
Red Blood Cells isotopic composition
Time frame: Baseline (day 7)
Red Blood Cells isotopic composition
Time frame: Day 35
Red Blood Cells isotopic composition
Time frame: Day 63
Red Blood Cells isotopic composition
Time frame: Day 98
Fecal calprotectin concentration
Time frame: Day 4-7 (baseline)
Fecal calprotectin concentration
Time frame: Day 32-35
Fecal calprotectin concentration
Time frame: Day 60-63
Fecal calprotectin concentration
Time frame: Day 95-98
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 27 Jul 2021.
- Background: PubMed 32862453Speich C, Wegmuller R, Brittenham GM, Zeder C, Cercamondi CI, Buhl D, Prentice AM, Zimmermann MB, Moretti D. Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe). Br J Haematol. 2021 Jan;192(1):179-189. doi: 10.1111/bjh.17039. Epub 2020 Aug 30.
- Derived from this study: PubMed 38302093Giorgetti A, Nyilima S, Stoffel NU, Moretti D, Mwasi E, Karanja S, Zeder C, Speich C, Netland C, Jin Z, Zimmermann MB, Brittenham GM. Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost. Br J Haematol. 2024 May;204(5):2057-2065. doi: 10.1111/bjh.19319. Epub 2024 Feb 1.
- 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.
Nicole U Stoffel, PhD principal investigator
ETH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferric ammonium citrate and ferrous fumarate syrup (Ranbaxy Ranferon-12 Syrup, Ranbaxy Laboratories, Gurgaon, India) in people with Iron Deficiency Anemia and Gastro Intestinal Bleeding, 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 8 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 27 Jul 2021. 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. 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?
Fecal occult blood concentration (time frame: Day 4-7 (baseline)). The study lists 4 primary outcomes in all. 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 NCT04721964, 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 27 Jul 2021.