The Efficacy of Zinc-biofortified Rice in Bangladeshi Children

Study Overview
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Brief Summary
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To assess the efficacy of the zinc biofortified rice on plasma zinc concentrations in infants from a rural area of Bangladesh.

Detailed Description
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Rationale: Around the world and estimated 30% of the population is at risk of Zinc deficiency, mainly due to monotonous plant base diets and the poor bioavailability of this sources. One staple food crop which is low in zinc content is rice. Therefore, zinc deficiency is highly common in Asia. Zinc plays a major role in child growth and neurobehavioral development. Furthermore, it is linked to infection control and normal immune response. One way to add extra zinc to someone's diet is zinc bio fortification of staple crops, which can be a cost saving sustainable approach to improve zinc nutrition. However, data on long-term intake of biofortified crops with zinc is scarce and efficacy of newly developed rice crops high in zinc are not well known. Objective: The objective is to assess the efficacy of a newly developed zinc biofortified rice variety on plasma zinc concentrations in children in a rural area of Bangladesh when compared to their controls in a 9 month randomized controlled trial (RCT). Study design: A double randomized control trial. Study population: Stunted children whom are zinc deficient at start of the study intervention determined by plasma zinc levels <9.9 µmol/L. Main study parameters/endpoints: The difference in zinc status between the intervention and control group expressed in blood plasma zinc levels. Plasma zinc will be measured 4 times during the intervention period. Besides plasma zinc other zinc biomarkers will be tested for their usefulness.

Official Title
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The Efficacy of Zinc-biofortified Rice in Improving Zinc Status in Young Bangladeshi Children, a Double Blind Randomized Controlled Trial

Conditions
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Zinc Deficiency, Growth; Stunting, Nutritional

Intervention / Treatment
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* Dietary Supplement: Intervention-group
* Dietary Supplement: Control-group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 12-36 months of age (at baseline assessment) Low plasma Zn concentration (<10.71 µmol/L) Marginally stunted (height for age Z-score <-1.75) 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: Severe Anemia (Hb< 70 g/L) Chronic or acute illness or other conditions that in the opinion of the Principle Investigator (PI) or co-researchers would affect Zn metabolism or would render the participant unable to comply with the protocol (based on self-reporting or diagnosed during screening) Participants taking part in other studies requiring the drawing of blood Not planning long-term residence in study site Regular intake (>2 days) of iron-containing mineral and vitamin supplements or fortified foods within the last 2 months Chronic use of drugs that affect the metabolism of Zn, including reducing absorption or increasing excretion; e.g., tuberculosis medications (ethambutal and isoniazides), drugs used as treatment for entamoeba hystolica (diiodohydroxyquin), drugs that reduce stomach acidity (H2 blockers and proton pump inhibitory), antidepressants (nialamide and socarboxazid), anti-inflammatory drugs (corticosteroids), diuretics (thiazides).

Ages Eligible for Study
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Minimum Age: 12 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: Control-group<br>Control Rice used for meal, normal zinc level | Dietary Supplement: Control-group<br>* Control Rice with normal zinc levels<br>|
| Active Comparator: Intervention-group<br>Biofortified Rice used for meal, around 30% higher zinc level | Dietary Supplement: Intervention-group<br>* Biofortified Rice is grown by foliar Zn application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma zinc | Change of plasma zinc values from baseline to endpoint and 2 times within study period | 4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers | C reactive protein (CRP),alpha1-acid glycoprotein (AGP) | 4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3). | 
| Length | Length (in cm) measurement for anthropometric (HAZ-scores). | 4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3). | 
| Weight | Weight (in kg) measurement for anthropometric (HAZ-scores). | 4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3). | 
| Morbidity | diarrhea and disease episodes will be recorded weekly throughout the study | Fixed assessment once a week for every participant throughout the intervention period (week 1-36). | 
| FADS analyses | FADS plasma analyses for zinc biomarker determination | Secondary analyses of collected plasma samples, in subset of participants (75 children from each group, random selected, matched baseline and endpoint samples) | 
| Iron status | Plasma ferritin | 4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3). | 
| Iron status | Hemoglobin | 4 collection points in total. 2 fixed at start and end of intervention (week 1&36, T=1,4). 2 sparse random sampling points (RSP) in-between T=1-4. First RSP between 2-5 months (week 5-20 T=2). Second RSP between 5-8 months (week 21-32,T=3). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zinc Biofortification, Zinc Status, Zinc Biomarker