The Effects of Iron Treatment on Malaria and Measles Vaccine Response in Kenyan Infants With Iron Deficiency

Malaria and iron deficiency cause a significant burden of disease in Africa. Iron deficiency (ID) might affect immune responses to vaccination.

In this double-blind randomized controlled trial, we aim to assess: (1) whether ID impairs R21/Matrix-M and measles (MR) vaccine response, (2) whether iron treatment at time of vaccination improves vaccine response.

Study Overview

• Status: Not yet recruiting
• Conditions: Iron Deficiencies
• Intervention / Treatment: Dietary supplement: Iron syrup; Dietary supplement: Multivitamin syrup; Biological: R21-Matrix/M Vaccine (malaria vaccine); Biological: Measles-Rubella vaccine

• Study Type: Interventional
• Enrollment (Estimated): 324
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicole Stoffel, PhD; Phone Number: +41 044 632 83 93; Email: nicole.stoffel@hest.ethz.ch
• Study Contact Backup: Name: Giulia Pironaci, MSc; Phone Number: +41 0799343770; Email: giulia.pironaci@rdm.ox.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject's caregiver is willing and able to give informed consent
• Male or Female, 6 months (+/- 2 weeks) of age
• Mother at least ≥15 years of age
• Iron deficient (erythrocyte zinc protoporphyrin (ZnPP) >61 μmol/mol heme)
• With or without anemia (anemia defined by Hb <110 g/L)

Exclusion Criteria:

• Severely anemic (Hb <70 g/L)
• Malaria vaccination prior to enrollment
• Medical condition that precludes study involvement
• Iron supplementation 2 weeks before enrollment
• Acute or chronic infection (e.g. HIV)
• Wasted (length for height z score of ≥-2) or underweight (weight for age z score ≥-2).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Iron treatment group; daily multivitamin + daily iron syrup from age 6 to 10 months	Dietary supplement: Iron syrup; Iron syrup administered daily from 6 to 10 months of age.; Dietary supplement: Multivitamin syrup; Multivitamin syrup administered daily from 6 to 10 months of age.; Biological: R21-Matrix/M Vaccine (malaria vaccine); R21-Matrix/M vaccine administered in 3 doses at 7, 8 and 9 months of age.; Biological: Measles-Rubella vaccine; Measles-Rubella vaccine administered at 9 months of age.
Other: Control group; daily multivitamin syrup from age 6 to 10 months	Dietary supplement: Multivitamin syrup; Multivitamin syrup administered daily from 6 to 10 months of age.; Biological: R21-Matrix/M Vaccine (malaria vaccine); R21-Matrix/M vaccine administered in 3 doses at 7, 8 and 9 months of age.; Biological: Measles-Rubella vaccine; Measles-Rubella vaccine administered at 9 months of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NANP-specific IgG	NANP-specific IgG	At 10 months of age (1 month after the 3rd R21/Matrix-M dose)
anti- full lengths CSP IgG	anti- full lenghts circumsporozoite protein IgG	At 10 months of age (1 month after the 3rd R21/Matrix-M dose)
anti- C-terminal CSP IgG	anti- full lenghts circumsporozoite protein IgG	At 10 months of age (1 month after the 3rd R21/Matrix-M dose)
anti-measles IgG	anti-measles IgG titre	At 10 months of age (1 month after the first MR dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NANP-specific IgG	NANP-specific IgG	At 8 months age (1 month after the first R21/Matrix-M dose)
NANP-specific IgG	NANP-specific IgG	At 9 months age (1 month after the second R21/Matrix-M dose)
anti- full lengths CSP IgG	anti- full lengths circumsporozoite protein IgG	At 8 months age (1 month after the first R21/Matrix-M dose)
anti- full lengths CSP IgG	anti- full lengths circumsporozoite protein IgG	At 9 months age (1 month after the second R21/Matrix-M dose)
anti-CSP IgA	anti- circumsporozoite protein IgA titre	At 8 months age (1 month after the first R21/Matrix-M dose)
anti-CSP IgA	anti-circumsporozoite protein IgA titre	At 9 months age (1 month after the second R21/Matrix-M dose)
anti-CSP IgM	anti circumsporozoite protein IgM titre	At 8 months age (1 month after the first R21/Matrix-M dose)
anti-CSP IgM	anti-circumsporozoite protein IgM titre	At 9 months age (1 month after the second R21/Matrix-M dose)
Haemoglobin	Haemoglobin concentration (g/dL)	6 months of age
Haemoglobin	Haemoglobin concentration (g/dL)	7 months of age
Haemoglobin	Haemoglobin concentration (g/dL)	8 months of age
Haemoglobin	Haemoglobin concentration (g/dL)	9 months of age
Haemoglobin	Haemoglobin concentration (g/dL)	10 months of age
Plasma iron	Plasma iron concentration (μg/mL)	6 months of age
Plasma iron	Plasma iron concentration (μg/mL)	7 months of age
Plasma iron	Plasma iron concentration (μg/mL)	8 months of age
Plasma iron	Plasma iron concentration (μg/mL)	9 months of age
Plasma iron	Plasma iron concentration (μg/mL)	10 months of age
Total iron binding capacity	Total iron binding capacity (mcd/dL)	6 months of age
Total iron binding capacity	Total iron binding capacity (mcd/dL)	7 months of age
Total iron binding capacity	Total iron binding capacity (mcd/dL)	8 months of age
Total iron binding capacity	Total iron binding capacity (mcd/dL)	9 months of age
Total iron binding capacity	Total iron binding capacity (mcd/dL)	10 months of age
Transferrin saturation	Transferrin saturation (%)	6 months of age
Transferrin saturation	Transferrin saturation (%)	7 months of age
Transferrin saturation	Transferrin saturation (%)	8 months of age
Transferrin saturation	Transferrin saturation (%)	9 months of age
Transferrin saturation	Transferrin saturation (%)	10 months of age
Plasma Ferritin	Plasma Ferritin concentration (μg/mL)	6 months of age
Plasma Ferritin	Plasma Ferritin concentration (μg/mL)	7 months of age
Plasma Ferritin	Plasma Ferritin concentration (μg/mL)	8 months of age
Plasma Ferritin	Plasma Ferritin concentration (μg/mL)	9 months of age
Plasma Ferritin	Plasma Ferritin concentration (μg/mL)	10 months of age
Soluble transferrin receptor	Soluble transferrin receptor concentration (μg/mL)	6 months of age
Soluble transferrin receptor	Soluble transferrin receptor concentration (μg/mL)	7 months of age
Soluble transferrin receptor	Soluble transferrin receptor concentration (μg/mL)	8 months of age
Soluble transferrin receptor	Soluble transferrin receptor concentration (μg/mL)	9 months of age
Soluble transferrin receptor	Soluble transferrin receptor concentration (μg/mL)	10 months of age
C-reactive protein	C-reactive protein concentration (mg/L)	6 months of age
C-reactive protein	C-reactive protein concentration (mg/L)	7 months of age
C-reactive protein	C-reactive protein concentration (mg/L)	8 months of age
C-reactive protein	C-reactive protein concentration (mg/L)	9 months of age
C-reactive protein	C-reactive protein concentration (mg/L)	10 months of age
Retinol-binding protein	Retinol-binding protein concentration (μmol/L)	6 months of age
Retinol-binding protein	Retinol-binding protein concentration (μmol/L)	7 months of age
Retinol-binding protein	Retinol-binding protein concentration (μmol/L)	8 months of age
Retinol-binding protein	Retinol-binding protein concentration (μmol/L)	9 months of age
Retinol-binding protein	Retinol-binding protein concentration (μmol/L)	10 months of age
Alpha-glycoprotein	Alpha-glycoprotein concentration (g/L)	6 months of age
Alpha-glycoprotein	Alpha-glycoprotein concentration (g/L)	7 months of age
Alpha-glycoprotein	Alpha-glycoprotein concentration (g/L)	8 months of age
Alpha-glycoprotein	Alpha-glycoprotein concentration (g/L)	9 months of age
Alpha-glycoprotein	Alpha-glycoprotein concentration (g/L)	10 months of age
anti- C-terminal CSP IgG	anti- C-terminal circumsporozoite protein IgG	At 8 months age (1 month after the first R21/Matrix-M dose)
anti- C-terminal CSP IgG	anti- C-terminal circumsporozoite protein IgG	At 9 months age (1 month after the second R21/Matrix-M dose)
anti-CSP IgA	anti-circumsporozoite protein IgA titre	At 10 months age (1 month after the 3rd R21/Matrix-M dose)
anti-CSP IgM	anti-circumsporozoite protein IgM titre	At 10 months age (1 month after the 3rd R21/Matrix-M dose)
anti-measles IgG avidity	anti-measles IgG avidity	At 10 months age (1 month after the first MR dose)

Collaborators and Investigators

• Sponsor: Nicole Stoffel
• Collaborators: National Institute for Public Health and the Environment (RIVM); Jomo Kenyatta University of Agriculture and Technology; Faculty of Medical Sciences, Radboud University of Medical Center; University of Oxford - Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
• Investigators: Principal Investigator: Nicole Stoffel, PhD, ETH Zurich

Study record dates

Study Major Dates

• Study Start (Estimated): January 5, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): February 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Malaria; Measles; Iron deficiency; Vaccine immunogenicity
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Metabolic Diseases; Infections; RNA Virus Infections; Virus Diseases; Protozoan Infections; Parasitic Diseases; Iron Metabolism Disorders; Paramyxoviridae Infections; Mononegavirales Infections; Morbillivirus Infections; Nutritional and Metabolic Diseases; Iron Deficiencies; Malaria; Measles; Biological Products; Complex Mixtures; Vaccines; Protozoan Vaccines; Malaria Vaccines
• Other Study ID Numbers: MEMA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No