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

Study Overview
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Brief Summary
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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.

Official Title
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Effects of Oral Iron Supplementation Before vs. at Time of Vaccination on Immune Response in Iron Deficient Kenyan Women

Conditions
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Iron Deficiency Anemia

Intervention / Treatment
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* Dietary Supplement: Oral iron supplementation (pre-treatment)
* Biological: COVID-19 vaccine
* Biological: MenACWY vaccine
* Dietary Supplement: Oral iron supplementation (simultaneous treatment)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Pregnant (confirmed by rapid test during screening) or lactating. Malaria (confirmed by rapid test) à study start will be postponed

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre-treatment group<br>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)<br>* Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 1-56<br>Biological: COVID-19 vaccine<br>* Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants<br>Biological: MenACWY vaccine<br>* MenACWY vaccination given on day 28 to all participants<br>|
| Experimental: Simultaneous treatment group<br>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<br>* Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants<br>Biological: MenACWY vaccine<br>* MenACWY vaccination given on day 28 to all participants<br>Dietary Supplement: Oral iron supplementation (simultaneous treatment)<br>* Iron supplements as 200 mg oral iron as FeSO4 given on alternate day on days 28-56<br>|
| Placebo Comparator: Control group<br>Participants assigned to this group will receive placebo on alternate days on study days 1-56. | Biological: COVID-19 vaccine<br>* Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants<br>Biological: MenACWY vaccine<br>* MenACWY vaccination given on day 28 to all participants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron deficiency, Anemia, Vaccine response, Women of reproductive age