Clinical trial NCT04137354: Iron and Vitamin A in School Children
Official title: Effects of Intermittent Iron and Vitamin A Supplementation on Nutritional Status and Development of Schoolchildren in Arba Minch Zuria District, Ethiopia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anemia, Iron Deficiency
Vitamin A Deficiency
Cognitive Development
Helminthic Infection
Keywords: Intermittent Iron supplementation
Vitamin A
Cognitive Development
Anemia
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Flemish Interuniversity Council (VLIR)
name: Arba Minch University
First posted: 2019-10-24
Enrollment: 504
Sex: ALL
Minimum age (years): 7
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: In randomized placebo-control trial eligible primary school children in the Arba Minch HDSS will be randomly assigned to four groups of treatment in a factorial 2x2 design:

1. A control placebo receiving placebo vitamin A at baseline and after 5 months, and placebo iron supplement weekly;
2. A high dose vitamin A at baseline and after 5 months and weekly placebo iron supplement;
3. Weekly iron supplementation for 10 months and placebo vitamin A at baseline and after 5 months;
4. Combined weekly iron supplementation and high dose vitamin A at baseline and after 5 months.

At the end of the study, and if the results are positive, children who receive the placebo iron supplement will receive weekly iron supplementation (42mg of elemental iron once a week) for 10 months. Children in all the treatment groups remain eligible to benefit from the standard health care and nutrition programs provided at school, such as deworming at the beginning of the school year
Primary purpose: PREVENTION

Brief summary: The WHO recommended intermittent iron supplementation as a strategy for prevention of anemia and iron deficiency among school age children. Several aspects of cognitive development, co-supplementation with other micronutrients, severe adverse events especially in the context of malaria were missing.

The investigators will evaluate the effectiveness of intermittent iron and vitamin A supplementation on cognitive development and anemia and iron status of Rural Ethiopian school children.

Detailed description: Iron deficiency is the commonest micronutrient deficiency worldwide and the major cause of specific anemia - iron deficiency anemia. Iron is an essential mineral with lots of functions in the human body; its deficiency is associated with cognitive impairment, emotional alteration, and altered homeostasis in myelination and neurotransmission. Vitamin A deficiency can lead to anemia, weakened resistance to infection, blindness, and death. Animal model studies showed that vitamin A could affect cognition. Cognitive skills, influenced by cognitive development of the individual, are related with academic performance of the student and long-term success. One target of the Sustainable Development Goals (SDG 4) is to ensure inclusive and equitable quality education and promote lifelong learning opportunities for all. Poor health and undernutrition of children in Low- and Middle-Income Countries (LMIC) are the major limitations to reach their potential school performance and learning skills. The evidence on the role of intermittent iron supplementation in preventing anemia is strong but several aspects of cognitive development, co-supplementation with other micronutrients such as vitamin A are missing.

The aim of this study is to evaluate the effectiveness of intermittent iron and high-dose vitamin A supplementation integrated within school nutritional plan on anemia, iron status and cognitive development of school children (7 - 10 year old) who live in areas with high rates of food insecurity in Ethiopia.

Method: The study will be carried out at primary schools in Arba Minch Zuria District, Ethiopia in children aged from 7 to 10 years. Eligible children (a total of 504 children) will be randomly assigned to one of the four groups: 1) Control placebo receiving placebo vitamin A and placebo iron supplement; 2) Vitamin A group will receive a high dose vitamin A capsule (200,000 IU) and placebo iron supplement.;3) Iron group will receive weekly iron supplementation (42 mg of elemental iron) and placebo vitamin A; and 4)Iron-vitamin A group will receive a combined weekly iron supplementation and high dose vitamin A.

Iron supplements (42mg of elemental iron)/placebo will be given to school chidlren weekly for 10 months and 200,000 IU of vitamin A/placebo will be given at baseline and after 5 months.

Eligibility criteria: Inclusion Criteria:

* One or both their parents signed informed consent form;
* Their parents planned to stay during the period of the study (for the full academic year) in the kebele; and
* They accept of the intervention package including blood draw and home visits. School children with severe anemia (Hb concentration \<80 g/L) will be treated by conventional protocol for three months at nearby health centres. After reassessing their haemoglobin concentrations, they can be assigned to their intervention groups if they become eligible as described above.

Exclusion Criteria:

* Chronically ill children like diagnosed diabetic and asthma
* Severely under nourished children (defined as body mass index z-score \<-3 standard deviations of the median WHO reference population)
* Those who are treated for tuberculosis or suspected to have tuberculosis
* Children with diagnosed haemoglobinopathy (sickle cell and thalassemias)
* Children with night blindness

Primary outcomes:
measure: Memory span
timeFrame: Memory span of the children will be assessed at 9 months
measure: Spatial exploration and awareness
timeFrame: Spatial exploration and awareness of the children will be assessed at 9 months
measure: Reasoning ability
timeFrame: The reasoning ability of the children will be assessed at 9 months
measure: Anemia
timeFrame: Hemoglobin concentrations of children will be assessed at 9 months
measure: Plasma ferritin
timeFrame: Plasma ferritin is assessed in all children at 9 months
measure: Soluble transferrin receptor
timeFrame: Soluble transferrin receptor is assessed in all children at 9 months
Secondary outcomes:
measure: Serum concentrations in Vitamin A (retinol)
timeFrame: Retinol concentrations will be assessed in all children at 9 months
measure: Serum concentrations in vitamin B12
timeFrame: Vitamin B12 concentrations will be assessed in all children at 9 months
measure: Prevalence of soil-transmitted helminths
timeFrame: The prevalence of soil-transmitted helminths will be assessed at 4.5 months and at 9 months
measure: Prevalence of Schistosome infection
timeFrame: Prevalence of Schistosome infection will be assessed at 4.5 months and at 9 months
measure: Adherence to the iron/placebo supplements
timeFrame: Weekly for the whole period of the intervention of 9 months.
Other outcomes:
Locations:
city: Arba Minch
country: Ethiopia
facility: Arba Minch University
Study officials:
affiliation: University Ghent
name: Stefaan De Henauw, Md. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Guideline: Intermittent Iron Supplementation in Preschool and School-Age Children. Geneva: World Health Organization; 2011. Available from http://www.ncbi.nlm.nih.gov/books/NBK179850/
citation: De-Regil LM, Jefferds ME, Sylvetsky AC, Dowswell T. Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD009085. doi: 10.1002/14651858.CD009085.pub2.
citation: Friis H, Mwaniki D, Omondi B, Muniu E, Magnussen P, Geissler W, Thiong'o F, Michaelsen KF. Serum retinol concentrations and Schistosoma mansoni, intestinal helminths, and malarial parasitemia: a cross-sectional study in Kenyan preschool and primary school children. Am J Clin Nutr. 1997 Sep;66(3):665-71. doi: 10.1093/ajcn/66.3.665.
citation: Zimmermann MB, Biebinger R, Rohner F, Dib A, Zeder C, Hurrell RF, Chaouki N. Vitamin A supplementation in children with poor vitamin A and iron status increases erythropoietin and hemoglobin concentrations without changing total body iron. Am J Clin Nutr. 2006 Sep;84(3):580-6. doi: 10.1093/ajcn/84.3.580.
citation: Mwaniki D, Omondi B, Muniu E, Thiong'o F, Ouma J, Magnussen P, Geissler PW, Michaelsen KF, Friis H. Effects on serum retinol of multi-micronutrient supplementation and multi-helminth chemotherapy: a randomised, controlled trial in Kenyan school children. Eur J Clin Nutr. 2002 Jul;56(7):666-73. doi: 10.1038/sj.ejcn.1601376.