Efficacy of Yellow Cassava to Improve Vitamin A Status of Kenyan School Children

Study Overview
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Brief Summary
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The overall aim of the project is to provide proof-of-principle that biofortification of cassava with vitamin A is a viable strategy to improve vitamin A status of deficient populations.

Detailed Description
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Rationale: Vitamin A deficiency is still common in developing countries and has been proven difficult to combat. A promising approach is to replace common crops with varieties that are naturally richer in vitamin A, which is referred to as biofortification. For cassava, yellow β-carotene rich varieties have recently been introduced in Kenya, and these varieties are now ready to be tested for their efficacy to improve vitamin A status in humans. Objective: The primary objective is to measure the effect of daily consumption of provitamin A biofortified cassava (providing 50% of the age-specific RDA) on vitamin A status in children aged 5-13 years with mild to moderate vitamin A deficiency in Kenya. To determine the bioefficacy of provitamin A carotenoids from biofortified cassava relative to that of a daily B-carotene supplement (comparison with positive control group). Secondary objectives are: 1) to measure the effect of the intervention on immune function indicators and morbidity; 2) to determine to what degree the serum retinol response to the intervention depends on serum concentrations of retinol and zinc at baseline; 3) to determine the effect of the intervention on functional indicators such as dark adaptation capacity, gut integrity, hematology indicators and thyroid status; 4) to determine the mediating effect of SNP's in the BCMO1 gene on treatment outcome. Study design & Study population : In this randomized controlled trial, school children aged 5-13 years living in the Kibwezi area, Kenya. Children will be selected from three (or four) primary schools in the area that have been pre-selected based on the prevalence of vitamin A deficiency, location and willingness to participate. Intervention: After screening for eligibility and a 2-week run-in period (n=360) Children will be randomly allocated to three different treatments: 1) 400 g of yellow cassava providing  50% of the RDA for vitamin A; and a placebo capsule; 2) 400 g of white cassava; and a placebo capsule; 3) 400 g of white cassava and a capsule containing 100 RAE of all-trans β-carotene. Main study parameters/endpoints: The main outcome measure will be differences in serum retinol concentrations between groups. Other outcome measures include other vitamin A status indicators (β-carotene, retinol binding protein, transthyretin), immune function indicators, dark adaptation, iron status indicators, anthropometrics, gut integrity, and thyroid function.

Official Title
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Efficacy of Yellow Cassava to Improve Vitamin A Status of Mildly Deficient Primary School Children in Kenya: a Randomized Controlled Trial

Conditions
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Vitamin A Deficiency

Intervention / Treatment
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* Other: Yellow cassava
* Other: White cassava
* Other: White cassava


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Low vitamin A status (retinol binding protein (RBP) at the lowest end of the distribution will be included in the study) Exclusion Criteria: History or signs of infectious or systemic diseases (e.g. tuberculosis, sickle cell anaemia) Anaemia, malaria or acute inflammation at the day of baseline measurements

Ages Eligible for Study
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Minimum Age: 61 Months
Maximum Age: 13 Years

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 |
| --- | --- |
| Experimental: Yellow cassava + placebo capsule<br> | Other: Yellow cassava<br>* Daily provision of 375 g boiled yellow cassava for 18 weeks, 6 days/week Daily provision of placebo capsule for 18 weeks, 6 days/week<br>|
| Placebo Comparator: White cassava + placebo capsule<br> | Other: White cassava<br>* Daily provision of 375 g boiled white cassava for 18 weeks, 6 days/ week Daily provision of placebo capsule for 18 weeks, 6 days/ week<br>|
| Active Comparator: White cassava + B-carotene capsule<br> | Other: White cassava<br>* Daily provision of 375 g boiled white cassava for 18 weeks, 6 days/week Daily provision of B-carotene capsule (1400 µg B-carotene)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum retinol concentration |  | Baseline, end of study (4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune function indicators | neopterin, IL-2, IL4, IL10, IL13, TNF-a, IFN-γ, TGF-β in serum; IgA in saliva | End of study (4 months) | 
| Bioefficacy | Comparison of change in serum retinol between yellow cassava group and positive control (B-carotene supplement group) | Baseline, end of study (4 months) | 
| Functional indicators | Gut integrity, dark adaptation, morbidity | End of study (4 months) | 
| Thyroid function | Serum Tg, TSH | End of study (4 months | 
| Effect modification | Serum zinc, serum retinol, iron status, polymorphisms | Baseline | 
| Anemia | Hemoglobin | End of study (4 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin A deficiency, Biofortification, Cassava, B-carotene, School children, Kenya