Iron and Vitamin A in School Children

NCT04137354 | Completed

• 1 other identifier: EC/2019/1289
• Study Type: interventional
• Target: 504
• Locations: 1 country
• Sites: 1

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.

Conditions

Anemia, Iron Deficiency; Vitamin A Deficiency; Cognitive Development; Helminthic Infection

Keywords

Intermittent Iron supplementation; Vitamin A; Cognitive Development; Anemia

Outcome Measures

Primary Outcomes (6)

• Memory span

  Digit span (forward and backward) is a standardized test that assess the working memory of the children, one indicator of cognitive development

  Memory span of the children will be assessed at 9 months

• Spatial exploration and awareness

  Vision search using cancellation task of the children, the second indicator of cognitive development

  Spatial exploration and awareness of the children will be assessed at 9 months

• Reasoning ability

  Raven's colored progressive matrices, the third indicator of cognitive development

  The reasoning ability of the children will be assessed at 9 months

• Anemia

  Hemoglobin concentrations (g/dL)

  Hemoglobin concentrations of children will be assessed at 9 months

• Plasma ferritin

  Iron status as indicated plasma ferritin (micro\_g/L) is a test to evaluate iron stores

  Plasma ferritin is assessed in all children at 9 months

• Soluble transferrin receptor

  Soluble transferrin receptor (mg/L) is an indicator for iron deficiency especially in high inflammation settings

  Soluble transferrin receptor is assessed in all children at 9 months

Secondary Outcomes (5)

• Serum concentrations in Vitamin A (retinol)

  Retinol concentrations will be assessed in all children at 9 months

• Serum concentrations in vitamin B12

  Vitamin B12 concentrations will be assessed in all children at 9 months

• Prevalence of soil-transmitted helminths

  The prevalence of soil-transmitted helminths will be assessed at 4.5 months and at 9 months

• Prevalence of Schistosome infection

  Prevalence of Schistosome infection will be assessed at 4.5 months and at 9 months

• Adherence to the iron/placebo supplements

  Weekly for the whole period of the intervention of 9 months.

Study Arms (4)

Control Iron&Vitamin A Placebo

PLACEBO COMPARATOR

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; Other: Placebo Vitamin A

Vitamin A & Placebo Iron Supplements

EXPERIMENTAL

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; Other: High-dose Vitamin A supplement

Intermittent Iron Supplements & Placebo Vitamin A

EXPERIMENTAL

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; Other: Placebo Vitamin A

Intermittent Iron Supplements & High dose Vitamin A

EXPERIMENTAL

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; Other: High-dose Vitamin A supplement

Interventions

Intermittent placebo iron supplement OTHER

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)

Also known as: Control iron

Control Iron&Vitamin A Placebo; Vitamin A & Placebo Iron Supplements

Intermittent iron supplement OTHER

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)

Also known as: Experimental iron

Intermittent Iron Supplements & High dose Vitamin A; Intermittent Iron Supplements & Placebo Vitamin A

Placebo Vitamin A OTHER

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).

Also known as: Control Vitamin A

Control Iron&Vitamin A Placebo; Intermittent Iron Supplements & Placebo Vitamin A

High-dose Vitamin A supplement OTHER

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).

Also known as: Experimental Vitamin A

Intermittent Iron Supplements & High dose Vitamin A; Vitamin A & Placebo Iron Supplements

Eligibility Criteria

• Age: 7 Years - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Ghent: lead
• Flemish Interuniversity Council (VLIR): collaborator
• Arba Minch University: collaborator

Study Sites (1)

Arba Minch University

Arba Minch, Ethiopia

Location

Related Publications (7)

• 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/

  PMID: 24479203 BACKGROUND

• 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.

  PMID: 22161444 BACKGROUND

• 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.

  PMID: 9280190 BACKGROUND

• 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.

  PMID: 16960172 BACKGROUND

• 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.

  PMID: 12080408 BACKGROUND

• Gutema BT, Tariku EZ, Melketsedik ZA, Levecke B, De Henauw S, Abubakar A, Abbeddou S. Assessing the influence of COVID-19 lockdown measures on cognition and behavior in school age children in Arba Minch Health and Demographic Surveillance site, Southern Ethiopia: A cross-sectional study. PLOS Glob Public Health. 2024 Mar 21;4(3):e0002978. doi: 10.1371/journal.pgph.0002978. eCollection 2024.

  PMID: 38512931 DERIVED

• Gutema BT, Levecke B, Sorrie MB, Megersa ND, Zewdie TH, Yesera GE, De Henauw S, Abubakar A, Abbeddou S. Effectiveness of intermittent iron and high-dose vitamin A supplementation on cognitive development of school children in southern Ethiopia: a randomized placebo-controlled trial. Am J Clin Nutr. 2024 Feb;119(2):470-484. doi: 10.1016/j.ajcnut.2023.11.005. Epub 2023 Nov 11.

  PMID: 37952928 DERIVED

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Vitamin A Deficiency; Trematode Infections; Anemia

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Helminthiasis; Parasitic Diseases; Infections

Study Officials

• Stefaan De Henauw, Md. PhD

  University Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 24, 2019
• Study Start: November 2, 2020
• Primary Completion: December 28, 2021
• Study Completion: December 28, 2021
• Last Updated: March 3, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ET (1)