Iron Status in Infants in Ethiopia.

Study Overview
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Brief Summary
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To assess the impact of soil iron intake from teff flour on iron status in infants in Debre Zeit, Ethiopia.

Detailed Description
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Rationale: Teff (Eragrostis Teff), a major staple crop in several areas of Ethiopia, is of special relevance to Fe biofortifcation as it provides the population with a regular high consumption of contaminant soil Fe due to the traditional threshing procedure under the hooves of the cattle. The bioavailability of soil Fe, and hence its contribution to Fe requirements, is unknown. Data on the bioavailability of soil Fe would clarify to what extent the soil Fe can be considered as a source of absorbable Fe. This information is important in order to establish dietary advice and is essential for the development of iron biofortification (and fortification) policies related to Fe nutrition in Ethiopia. Objective: The overall objective of the project is to generate data to target and tailor biofortification approaches in Ethiopia by an intervention trial assessing the impact of soil Fe intake from teff consumption on Fe status. Study design: The intervention trial will be a 7 months partially blinded, randomized control trial (RCT) with the following three arms: control-group consuming injera based on traditionally threshed teff (average Fe content 50 mg/100g flour), 2) intervention group consuming injera based on lab-threshed teff (average Fe content 6.65 mg/100g flour), 3) positive control group consuming the lab-threshed teff together with ferrous sulphate iron drops (additional Fe from the drops = 6 mg). Study population: 315 children between 18-36 months of age living in Debre Zeit and surrounding areas will be enrolled. Main study parameters/endpoints: The impact of soil Fe in teff on Fe status will be assessed by measuring the Fe status, prevalence of Fe deficiency and Fe deficiency anemia at baseline, midpoint and endpoint. To assess Fe status, Hemoglobin (Hb), Plasma Ferritin (PF), Soluble Transferrin Receptor (sTfR), C- Reactive Protein(CRP) and Alpha 1B glycoprotein (AGP) will be determined.

Official Title
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Assessing the Impact of Soil Iron Intake From Teff Flour on Iron Status in Infants in Ethiopia.

Conditions
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Iron-deficiency, Iron Deficiency Anemia, Aluminium Intoxication

Intervention / Treatment
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* Other: Traditionally Threshed Teff (TTT)
* Other: Lab Threshed Teff (LTT)
* Other: Fortified Lab Threshed Teff (FTT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-36 months of age (at screening) The child is able to eat at least two injera meals per day The informed consent form has been read and signed by the caregiver (or has been read out to the caregiver in case of illiteracy) Exclusion Criteria: Severely deficient in Hb (<70g/L) Severe underweight (weight for age Z score < -3), Severe wasting (weight for height Z score < -3) Chronic or acute illness or other conditions that in the opinion of the Principle Investigator (PI) 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 Not planning long-term residence in study site

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Traditionally Threshed Teff (TTT)<br>The control group will consume injera based on teff threshed under the hooves of cattle. We plan to have a certain number of teff flour suppliers, where the teff is traditionally threshed and contains at least 50 mg Fe per 100 g flour. | Other: Traditionally Threshed Teff (TTT)<br>* The intervention will take place for 7 months in Debre Zeit where the the arm will be fed injera based on teff that are threshed traditionally<br>|
| Experimental: Lab Threshed Teff (LTT)<br>The intervention group will consume injera based on teff flour that has been lab threshed using a modern teff threshing machine. | Other: Lab Threshed Teff (LTT)<br>* The intervention will take place for 7 months in Debre Zeit where this arm will be fed injera from teff that is threshed using a modern thresher.<br>|
| Active Comparator: Fortified Lab Threshed Teff (FTT)<br>This arm will be the positive control group consuming Ferrous Sulphate drops ( with injera that consist of lab-threshed teff. The Fe drops have to be consumed with the meal and will provide an additional 6 mg of Ferrous sulfate to the diet of the children. | Other: Fortified Lab Threshed Teff (FTT)<br>* The intervention will take place for 7 months in Debre Zeit where this arm will be fed injera from teff that is threshed using a modern thresher. In addition, they will receive Ferrous sulfate drops<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Haemoglobin | Iron status | Three collection points - First collection point at screening, second collection point at mid point (3.5 months after start of intervention) and third collection point at the end point ( end of the 7 months of the intervention) | 
| Change in Ferritin | Iron status | Two collection points - First collection point at screening, second collection point at the end of the study ( 7 months after the intervention start ) | 
| Change in Soluble Transferrin Receptor (sTfR) | Iron status | Two collection points - First collection point at screening, second collection point at the end of the study ( 7 months after the intervention start ) | 
| Change in C-Reactive Protein (CRP) | Inflammation | Two collection points - First collection point at screening, second collection point at the end of the study ( 7 months after the intervention start ) | 
| Change in Alpha 1-Acid Glycoprotein (AGP) | Inflammation | Two collection points - First collection point at screening, second collection point at the end of the study ( 7 months after the intervention start ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Aluminium (Al) levels | Measuring Al in plasma | Two collection points - First collection point at screening, second collection point at the end of the study ( 7 months after the intervention start ) | 
| Change in Aluminium (Al) levels | Measuring Al in hair and nail | Three collection points - First collection point at the first day of the study, Second collection point during mid point ( 3.5 months after start of the intervention, and third collection point at the end of the intervention ( end of 7th month) | 
| Change in Anthropometric measurements | Weight in kg | Three collection points - First collection point during screening, Second collection point during mid point ( 3.5 months after start of the intervention, and third collection point at the end of the intervention ( end of 7th month) | 
| Change in Anthropometric measurements | Height in cm | Three collection points - First collection point during screening, Second collection point during mid point ( 3.5 months after start of the intervention, and third collection point at the end of the intervention ( end of 7th month) | 
| Teff flour | Iron concentration | Through study completion, an average of 7 months | 
| Teff flour | Phytate content | Through study completion, an average of 7 months | 
| Morbidity | Any sickness arising due to the consumption of the meals | Through study completion, an average of 7 months | 
| Injera consumption | Amount of injera consumed by the child in each meal | Through study completion, an average of 7 months | 
| 2 day weighted food record | To estimate the amount of different foods consumed by the child | Through study completion, an average of 7 months |