Effects of Oral Iron Supplementation on Vaccine Response in Iron Deficient Kenyan Women
Study Details
Study Description
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 Coronavirus disease 2019 (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 the participants' response; 2) the timing of oral iron treatment to improve vaccine response (prior to vaccination vs at time of vaccination).
The investigators will conduct a double-blind randomized controlled trial in southern Kenya to assess the effects of iron supplementation on response to two single-shot vaccines: Johnson & Johnson COVID- 19 (JJ COVID-19) and the quadrivalent meningococcal vaccine (MenACWY). Women with IDA will be recruited and randomly assigned to three study groups: group 1 (pre- treatment) will receive 200 mg oral iron as ferrous sulfate (FeSO4) on alternate days on days 1-56; group 2 (simultaneous treatment) will receive matching placebo on alternate days on days 1-28, and 200 mg oral iron as FeSO4 on alternate days on days 29-56; and group 3 (control) will receive matching placebo on alternate days on days 1-56. Women in all groups will receive the JJ COVID-19 vaccine and the MenACWY vaccine on day 28. Cellular immune response will be measured at 7 days after vaccination and serology will be measured at 28 days after vaccination in all groups.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pre-treatment group 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)
Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 1-56
Biological: COVID-19 vaccine
Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants
Biological: MenACWY vaccine
MenACWY vaccination given on day 28 to all participants
|
| Experimental: Simultaneous treatment group 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
Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants
Biological: MenACWY vaccine
MenACWY vaccination given on day 28 to all participants
Dietary Supplement: Oral iron supplementation (simultaneous treatment)
Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 28-56
|
| Placebo Comparator: Control group Participants assigned to this group will receive placebo on alternate days on study days 1-56. |
Biological: COVID-19 vaccine
Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants
Biological: MenACWY vaccine
MenACWY vaccination given on day 28 to all participants
|
Outcome Measures
Primary Outcome Measures
- Baseline anti-strike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2 [Day 28]
- Anti-S1 and anti-RBD IgG concentrations against SARS-COV-2 at study end [Day 56]
- Baseline IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [Day 28]
- Anti-MenACWY IgG concentrations at study end [Day 56]
Secondary Outcome Measures
- 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]
- Zinc protoporphyrin concentration (µmol/mol heme) at study end [Day 56]
- Plasma iron concentration (µg/mL) at baseline [Day 1]
- Plasma iron concentration (µg/mL) at time of vaccination [Day 28]
- Plasma iron concentration (µg/mL) at study end [Day 56]
- Total iron binding capacity at baseline [Day 1]
- Total iron binding capacity at time of vaccination [Day 28]
- Total iron binding capacity at study end [Day 56]
- Transferrin saturation (%) at baseline [Day 1]
- Transferrin saturation (%) at time of vaccination [Day 28]
- Transferrin saturation (%) at study end [Day 56]
- Plasma ferritin concentration (µg/L) at baseline [Day 1]
- Plasma ferritin concentration (µg/L) at time of vaccination [Day 28]
- Plasma ferritin concentration (µg/L) at study end [Day 56]
- Soluble transferrin receptor concentration (mg/L) at baseline [Day 1]
- Soluble transferrin receptor concentration (mg/L) at time of vaccination [Day 28]
- Soluble transferrin receptor concentration (mg/L) at study end [Day 56]
- C-reactive protein concentration (mg/L) at baseline [Day 1]
- C-reactive protein concentration (mg/L) at time of vaccination [Day 28]
- C-reactive protein concentration (mg/L) at study end [Day 56]
- Retinol binding protein concentration (µmol/L) at baseline [Day 1]
- Retinol binding protein concentration (µmol/L) at time of vaccination [Day 28]
- Retinol binding protein concentration (µmol/L) at study end [Day 56]
- Alpha-glycoprotein (AGP) concentration at baseline [Day 1]
- Alpha-glycoprotein concentration (g/L) at time of vaccination [Day 28]
- Alpha-glycoprotein concentration (g/L) at study end [Day 56]
- T-cell response assessed with an enzyme-linked immunosorbent assay (ELISA) detecting interferon-gamma (IFN-gamma) produced by T-helper cells (CD4+) and cytotoxic T cells (CD8+) responses to SARS-CoV-2 peptides at one week from vaccination [Day 35]
- T-cell response assessed with an enzyme-linked immunosorbent assay (ELISA) detecting IFN-gamma produced by CD4+ and CD8+ T cell responses to SARS-CoV-2 peptides at study end [Day 56]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing and able to give informed consent for participation in the trial
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Female aged 18-49 years
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Moderate anemia (Hb <110 g/L, but not severely anemic with Hb <80 g/L) • Iron deficient (ZnPP >40 mmol/mol haem)
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Anticipated residence in the study area for the study duration
Exclusion Criteria:
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Major chronic infectious disease (e.g., HIV infection);
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Major chronic non-infectious disease (e.g., Type 2 diabetes, cancer);
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Chronic medications;
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Use of iron-containing mineral and vitamin supplementation 2 weeks prior to study start;
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COVID-19 vaccine or confirmed COVID-19 infection within the past 2 years
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MenACWY vaccine in the past
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Pregnant (confirmed by rapid test during screening) or lactating.
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Malaria (confirmed by rapid test) à study start will be postponed
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Msambweni County Referral Hospital | Msambweni | Kenya | 80404 |
Sponsors and Collaborators
- Prof Simon Karanja
- Swiss Federal Institute of Technology
- University of Oxford
Investigators
- Principal Investigator: Simon Karanja, PhD, JKUAT
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DIVA_II