IronVitA: Iron and Vitamin A in School Children

Sponsor

University Ghent (Other)

Overall Status

Completed

CT.gov ID

NCT04137354

Collaborator

Flemish Interuniversity Council (VLIR) (Other), Arba Minch University, Ethiopia (Other)

504

Enrollment

Location

Arms

12.9

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Iron Deficiency Vitamin A Deficiency Cognitive Development Helminthic Infection	Other: Intermittent placebo iron supplement Other: Intermittent iron supplement Other: Placebo Vitamin A Other: High-dose Vitamin A supplement	N/A

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

504 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

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: A control placebo receiving placebo vitamin A at baseline and after 5 months, and placebo iron supplement weekly; A high dose vitamin A at baseline and after 5 months and weekly placebo iron supplement; Weekly iron supplementation for 10 months and placebo vitamin A at baseline and after 5 months; 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 yearIn 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:A control placebo receiving placebo vitamin A at baseline and after 5 months, and placebo iron supplement weekly; A high dose vitamin A at baseline and after 5 months and weekly placebo iron supplement; Weekly iron supplementation for 10 months and placebo vitamin A at baseline and after 5 months; 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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Iron supplements and their placebo: Both iron and placebo supplements will be produced by Metagenics (Belgium) for the context of this study. Placebo tablets will have the same taste, and shape of the iron tablets, the colour is slightly different because of the characteristics of the products but the blinding is ensured. The blister/ the tablets will be packed and only coded. Vitamin A and its placebo: Vitamin A capsule is oral liquid, red, oil-based preparation of retinyl palmitate that contains the equivalent of 100,000 IU (110μmol) of vitamin A and stabilized with 20IU of vitamin E. The placebo supplement will have the same oil composition except that it will not contain vitamin A equivalent. Placebo oil and vitamin A preparation will be transferred to two colored (red and orange) Eppendorf® Safe-Lock microcentrifuge tubes volume 0.6 mL by a researcher who is not involved in the study.

Primary Purpose:

Prevention

Official Title:

Effects of Intermittent Iron and Vitamin A Supplementation on Nutritional Status and Development of Schoolchildren in Arba Minch Zuria District, Ethiopia.

Actual Study Start Date :

Nov 2, 2020

Actual Primary Completion Date :

Nov 30, 2021

Actual Study Completion Date :

Nov 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Control Iron&Vitamin A Placebo Children randomly assigned to the placebo iron & vitamin A control group will receive weekly three placebo tablets that are identical to the iron tablets (blinded) for the whole duration of the study (9 months of the school year). They will also receive placebo vitamin A at baseline and at mid-line (after 4.5 months).	Other: Intermittent placebo iron supplement Placebo iron supplements are also three tablets containing the same ingredients as for iron tablets and will be given to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months) Other Names: Control iron Other: Placebo Vitamin A Children will receive in a colorful Eppendorf tube 400 micro-liter of corn oil stabilized with vitamin A twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months). Other Names: Control Vitamin A
Experimental: Vitamin A & Placebo Iron Supplements Children is this group will receive weekly three placebo tablets that are identical to the iron tablets (blinded) for the whole duration of the study (9 months of the school year). They will also receive a high dose vitamin A capsule (200,000IU) at baseline and after 4.5 months (at mid-line)	Other: Intermittent placebo iron supplement Placebo iron supplements are also three tablets containing the same ingredients as for iron tablets and will be given to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months) Other Names: Control iron Other: High-dose Vitamin A supplement Children will receive in a colorful Eppendorf tube 400 micro-liter of oil-based preparation of retinyl palmitate that contains the equivalent of 100,000 IU (110μmol) of vitamin A and stabilized with 20IU of vitamin E twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months). Other Names: Experimental Vitamin A
Experimental: Intermittent Iron Supplements & Placebo Vitamin A Children is this group will receive weekly three tablets of iron (42mg of elemental iron once a week) for 9 months (equivalent to a one school year). They will also receive placebo vitamin A at baseline and at mid-line (after 4.5 months).	Other: Intermittent iron supplement Three iron tablets containing 42 mg of elemental iron will be provided to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months) Other Names: Experimental iron Other: Placebo Vitamin A Children will receive in a colorful Eppendorf tube 400 micro-liter of corn oil stabilized with vitamin A twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months). Other Names: Control Vitamin A
Experimental: Intermittent Iron Supplements & High dose Vitamin A Combined weekly iron supplementation (42mg of elemental iron once a week) for 9 months and high dose vitamin A (200,000IU) at baseline and after 4.5 months (mid-line).	Other: Intermittent iron supplement Three iron tablets containing 42 mg of elemental iron will be provided to the children on a weekly basis for the whole duration of the intervention (i.e. the school year of 9 months) Other Names: Experimental iron Other: High-dose Vitamin A supplement Children will receive in a colorful Eppendorf tube 400 micro-liter of oil-based preparation of retinyl palmitate that contains the equivalent of 100,000 IU (110μmol) of vitamin A and stabilized with 20IU of vitamin E twice during the intervention period of 9 months, at baseline (after enrollment) and at mid-line (4.5 months). Other Names: Experimental Vitamin A

Outcome Measures

Primary Outcome Measures

Memory span [Memory span of the children will be assessed at 9 months]
Digit span (forward and backward) is a standardized test that assess the working memory of the children, one indicator of cognitive development
Spatial exploration and awareness [Spatial exploration and awareness of the children will be assessed at 9 months]
Vision search using cancellation task of the children, the second indicator of cognitive development
Reasoning ability [The reasoning ability of the children will be assessed at 9 months]
Raven's colored progressive matrices, the third indicator of cognitive development
Anemia [Hemoglobin concentrations of children will be assessed at 9 months]
Hemoglobin concentrations (g/dL)
Plasma ferritin [Plasma ferritin is assessed in all children at 9 months]
Iron status as indicated plasma ferritin (micro_g/L) is a test to evaluate iron stores
Soluble transferrin receptor [Soluble transferrin receptor is assessed in all children at 9 months]
Soluble transferrin receptor (mg/L) is an indicator for iron deficiency especially in high inflammation settings

Secondary Outcome Measures

Serum concentrations in Vitamin A (retinol) [Retinol concentrations will be assessed in all children at 9 months]
Retinol concentrations in serum is an indicator of vitamin A status of children
Serum concentrations in vitamin B12 [Vitamin B12 concentrations will be assessed in all children at 9 months]
Serum concentrations in vitamin B12
Prevalence of soil-transmitted helminths [The prevalence of soil-transmitted helminths will be assessed at 4.5 months and at 9 months]
The presence of worm parasites and egg density in the stools. Three common parasites and their eggs will be investigated, i.e. Ascaris lumbricoides (round worm), Trichuris trichiura (whipworm) and Ancyclostoma duodenale or Necater americanus (hookworms).
Prevalence of Schistosome infection [Prevalence of Schistosome infection will be assessed at 4.5 months and at 9 months]
The prevalence of Schistosoma mansoni infection
Adherence to the iron/placebo supplements [Weekly for the whole period of the intervention of 9 months.]
Adherence to the tablets of Iron/Placebo will be assessed through teacher's reports. Teachers are the ones who are providing the supplements in a weekly basis.

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years to 10 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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