Effects of Oral Iron Supplementation on Vaccine Response in Iron Deficient Kenyan Women
- Conditions
- Iron Deficiency Anemia
- Interventions
- Biological: COVID-19 vaccineDietary Supplement: Oral iron supplementation (pre-treatment)Biological: MenACWY vaccineDietary Supplement: Oral iron supplementation (simultaneous treatment)Biological: Typhim Vi vaccine
- Registration Number
- NCT05919472
- Lead Sponsor
- Prof Simon Karanja
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 180
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control group MenACWY vaccine Participants assigned to this group will receive placebo on alternate days on study days 1-56. Simultaneous treatment group Oral iron supplementation (simultaneous treatment) 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. Control group COVID-19 vaccine Participants assigned to this group will receive placebo on alternate days on study days 1-56. Control group Typhim Vi vaccine Participants assigned to this group will receive placebo on alternate days on study days 1-56. Simultaneous treatment group COVID-19 vaccine 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. Simultaneous treatment group MenACWY vaccine 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. Pre-treatment group Oral iron supplementation (pre-treatment) Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56. Pre-treatment group COVID-19 vaccine Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56. Pre-treatment group MenACWY vaccine Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56. Pre-treatment group Typhim Vi vaccine Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56. Simultaneous treatment group Typhim Vi vaccine 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.
- Primary Outcome Measures
Name Time Method 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 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
- Secondary Outcome Measures
Name Time Method Hemoglobin concentration (g/L) at study end Days 56 Zinc protoporphyrin concentration (µmol/mol heme) at study end Day 56 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 study end Day 56 Transferrin saturation (%) at baseline Day 1 Hemoglobin concentration (g/L) at baseline Day 1 Hemoglobin concentration (g/L) at time of vaccination Day 28 Total iron binding capacity at baseline Day 1 Total iron binding capacity at time of vaccination Day 28 Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination Day 28 Plasma iron concentration (µg/mL) at baseline Day 1 Plasma ferritin concentration (µg/L) at study end Day 56 Zinc protoporphyrin concentration (µmol/mol heme) at baseline Day 1 Soluble transferrin receptor concentration (mg/L) at time of vaccination Day 28 C-reactive protein concentration (mg/L) at baseline Day 1 C-reactive protein concentration (mg/L) at study end Day 56 Alpha-glycoprotein concentration (g/L) at study end Day 56 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 COVID-19 specific T cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying specific cytokines' concentration. Day 56 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 Soluble transferrin receptor concentration (mg/L) at baseline Day 1 Retinol binding protein concentration (µmol/L) at time of vaccination Day 28 Alpha-glycoprotein (AGP) concentration at baseline Day 1 Typhim Vi specific B-cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying antibodies' and memory B cell concentration. Day 56 Soluble transferrin receptor concentration (mg/L) at study end Day 56 C-reactive protein concentration (mg/L) at time of vaccination Day 28 Retinol binding protein concentration (µmol/L) at baseline Day 1 Retinol binding protein concentration (µmol/L) at study end Day 56 Alpha-glycoprotein concentration (g/L) at time of vaccination Day 28
Trial Locations
- Locations (1)
Msambweni County Referral Hospital
🇰🇪Msambweni, Kenya