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

Iron Deficiency Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05919472
• Other study ID #: DIVA_II
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2023
• Est. completion date: September 30, 2024

Study information

• Verified date: January 2024
• Source: Jomo Kenyatta University of Agriculture and Technology
• Contact: Giulia Pironaci, MSc
• Phone: +41 44 632 93 29
• Email: giulia.pironaci[@]rdm.ox.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: September 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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
• 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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron Deficiency Anemia

Intervention

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
• 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

Biological:
• Typhim Vi vaccine
Typhim Vi vaccination given on day 28 to all participants

Locations

Country	Name	City	State
Kenya	Msambweni County Referral Hospital	Msambweni

Sponsors (3)

Lead Sponsor	Collaborator
Prof Simon Karanja	Swiss Federal Institute of Technology, University of Oxford

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]		Day 56
Primary	IgG concentration against Typhoid [iU/ml]		Day 56
Secondary	Hemoglobin concentration (g/L) at baseline		Day 1
Secondary	Hemoglobin concentration (g/L) at time of vaccination		Day 28
Secondary	Hemoglobin concentration (g/L) at study end		Days 56
Secondary	Zinc protoporphyrin concentration (µmol/mol heme) at baseline		Day 1
Secondary	Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination		Day 28
Secondary	Zinc protoporphyrin concentration (µmol/mol heme) at study end		Day 56
Secondary	Plasma iron concentration (µg/mL) at baseline		Day 1
Secondary	Plasma iron concentration (µg/mL) at time of vaccination		Day 28
Secondary	Plasma iron concentration (µg/mL) at study end		Day 56
Secondary	Total iron binding capacity at baseline		Day 1
Secondary	Total iron binding capacity at time of vaccination		Day 28
Secondary	Total iron binding capacity at study end		Day 56
Secondary	Transferrin saturation (%) at baseline		Day 1
Secondary	Transferrin saturation (%) at time of vaccination		Day 28
Secondary	Transferrin saturation (%) at study end		Day 56
Secondary	Plasma ferritin concentration (µg/L) at baseline		Day 1
Secondary	Plasma ferritin concentration (µg/L) at time of vaccination		Day 28
Secondary	Plasma ferritin concentration (µg/L) at study end		Day 56
Secondary	Soluble transferrin receptor concentration (mg/L) at baseline		Day 1
Secondary	Soluble transferrin receptor concentration (mg/L) at time of vaccination		Day 28
Secondary	Soluble transferrin receptor concentration (mg/L) at study end		Day 56
Secondary	C-reactive protein concentration (mg/L) at baseline		Day 1
Secondary	C-reactive protein concentration (mg/L) at time of vaccination		Day 28
Secondary	C-reactive protein concentration (mg/L) at study end		Day 56
Secondary	Retinol binding protein concentration (µmol/L) at baseline		Day 1
Secondary	Retinol binding protein concentration (µmol/L) at time of vaccination		Day 28
Secondary	Retinol binding protein concentration (µmol/L) at study end		Day 56
Secondary	Alpha-glycoprotein (AGP) concentration at baseline		Day 1
Secondary	Alpha-glycoprotein concentration (g/L) at time of vaccination		Day 28
Secondary	Alpha-glycoprotein concentration (g/L) at study end		Day 56
Secondary	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
Secondary	COVID-19 specific T cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying specific cytokines' concentration.		Day 56
Secondary	Typhim Vi specific B-cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying antibodies' and memory B cell concentration.		Day 56