Effects of Oral Iron Supplementation on Vaccine Response in Iron Deficient Kenyan Women

NCT05919472 | Completed

• 1 other identifier: DIVA_II
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Iron deficiency (ID) anemia (IDA) is a global public health problem, with the highest prevalence in Africa. Vaccines often underperform in low- and middle- income countries (LMIC), and undernutrition, including ID, likely plays a role. Recent studies have shown the importance of iron status in vaccine response. Intravenous iron given at time of vaccination improved response to yellow fever and COVID-19 vaccines in IDA Kenyan women. Whether oral iron treatment would have a similar beneficial effect on vaccine response is uncertain. Also, timing of oral iron treatment needs further investigation. The co-primary objectives of this study are to assess 1) whether IDA in Kenyan women impairs vaccine response, and whether oral iron treatment improves their response; 2) the timing of oral iron treatment to improve vaccine response (prior to vaccination vs at time of vaccination). We will conduct a double-blind randomized controlled trial in southern Kenya to assess the effects of iron supplementation on response to three single-shot vaccines: Johnson \& Johnson COVID- 19 (JJ COVID-19), the quadrivalent meningococcal vaccine (MenACWY) and the typhoid Vi polysaccharide vaccine (Typhim Vi). Women with IDA will be recruited and randomly assigned to three study groups: group 1 (pre- treatment) will receive 100 mg oral iron as ferrous sulfate (FeSO4) daily on days 1-56; group 2 (simultaneous treatment) will receive matching placebo daily on days 1-28, and 200 mg oral iron as FeSO4 daily on days 29-56; and group 3 (control) will receive matching placebo daily on days 1-56. Women in all groups will receive the JJ COVID-19 vaccine, the MenACWY and the Typhim Vi vaccine on day 28. Cellular immune response and serology will be measured at 28 days after vaccination in all groups.

Conditions

Iron Deficiency Anemia

Keywords

Iron deficiency; Anemia; Vaccine response; Women of reproductive age

Outcome Measures

Primary Outcomes (3)

• anti-spike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2 [iU/ml]

  Day 56

• IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]

  Day 56

• IgG concentration against Typhoid [iU/ml]

  Day 56

Secondary Outcomes (33)

• Hemoglobin concentration (g/L) at baseline

  Day 1

• Hemoglobin concentration (g/L) at time of vaccination

  Day 28

• Hemoglobin concentration (g/L) at study end

  Days 56

• Zinc protoporphyrin concentration (µmol/mol heme) at baseline

  Day 1

• Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination

  Day 28

Study Arms (3)

Pre-treatment group

EXPERIMENTAL

Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.

Dietary Supplement: Oral iron supplementation (pre-treatment); Biological: COVID-19 vaccine; Biological: MenACWY vaccine; Biological: Typhim Vi vaccine

Simultaneous treatment group

EXPERIMENTAL

Participants assigned to this group will receive placebo on alternate days on study days 1-28 and 200 mg oral iron on alternate days on study days 29-56.

Biological: COVID-19 vaccine; Biological: MenACWY vaccine; Dietary Supplement: Oral iron supplementation (simultaneous treatment); Biological: Typhim Vi vaccine

Control group

PLACEBO COMPARATOR

Participants assigned to this group will receive placebo on alternate days on study days 1-56.

Biological: COVID-19 vaccine; Biological: MenACWY vaccine; Biological: Typhim Vi vaccine

Interventions

Oral iron supplementation (pre-treatment) DIETARY_SUPPLEMENT

Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 1-56

Pre-treatment group

COVID-19 vaccine BIOLOGICAL

Johnson \& Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants

Control group; Pre-treatment group; Simultaneous treatment group

MenACWY vaccine BIOLOGICAL

MenACWY vaccination given on day 28 to all participants

Control group; Pre-treatment group; Simultaneous treatment group

Oral iron supplementation (simultaneous treatment) DIETARY_SUPPLEMENT

Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 28-56

Simultaneous treatment group

Typhim Vi vaccine BIOLOGICAL

Typhim Vi vaccination given on day 28 to all participants

Control group; Pre-treatment group; Simultaneous treatment group

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to give informed consent for participation in the trial
• Female aged 18-49 years
• Moderate anemia (Hb \<110 g/L, but not severely anemic with Hb \<80 g/L) • Iron deficient (ZnPP \>40 mmol/mol haem)
• Anticipated residence in the study area for the study duration

You may not qualify if:

• Major chronic infectious disease (e.g., HIV infection);
• Major chronic non-infectious disease (e.g., Type 2 diabetes, cancer);
• Chronic medications;
• Use of iron-containing mineral and vitamin supplementation 2 weeks prior to study start;
• COVID-19 vaccine or confirmed COVID-19 infection within the past 2 years
• MenACWY vaccine in the past
• Typhoid vaccine in the past
• Pregnant (confirmed by rapid test during screening) or lactating.
• Malaria (confirmed by rapid test) à study start will be postponed

Sponsors & Collaborators

• Nicole Stoffel: lead
• Swiss Federal Institute of Technology: collaborator
• University of Oxford: collaborator

Study Sites (1)

Msambweni County Referral Hospital

Msambweni, 80404, Kenya

Location

MeSH Terms

Conditions

Anemia, Iron-Deficiency; Iron Deficiencies; Anemia

Interventions

COVID-19 Vaccines; Vi polysaccharide vaccine, typhoid

Condition Hierarchy (Ancestors)

Anemia, Hypochromic; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Simon Karanja, PhD

  JKUAT

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 26, 2023
• Study Start: July 1, 2023
• Primary Completion: July 16, 2024
• Study Completion: July 16, 2024
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1)