Clinical trial NCT05919472: Effects of Oral Iron Supplementation on Vaccine Response in Iron Deficient Kenyan Women
Official title: Effects of Oral Iron Supplementation Before vs. at Time of Vaccination on Immune Response in Iron Deficient Kenyan Women
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Iron Deficiency Anemia
Keywords: Iron deficiency
Anemia
Vaccine response
Women of reproductive age
Lead sponsor: Jomo Kenyatta University of Agriculture and Technology
Sponsor class: OTHER
Collaborators: name: Swiss Federal Institute of Technology
name: University of Oxford
First posted: 2023-06-26
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: anti-spike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2 [iU/ml]
timeFrame: Day 56
measure: IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]
timeFrame: Day 56
measure: IgG concentration against Typhoid [iU/ml]
timeFrame: Day 56
Secondary outcomes:
measure: Hemoglobin concentration (g/L) at baseline
timeFrame: Day 1
measure: Hemoglobin concentration (g/L) at time of vaccination
timeFrame: Day 28
measure: Hemoglobin concentration (g/L) at study end
timeFrame: Days 56
measure: Zinc protoporphyrin concentration (µmol/mol heme) at baseline
timeFrame: Day 1
measure: Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination
timeFrame: Day 28
measure: Zinc protoporphyrin concentration (µmol/mol heme) at study end
timeFrame: Day 56
measure: Plasma iron concentration (µg/mL) at baseline
timeFrame: Day 1
measure: Plasma iron concentration (µg/mL) at time of vaccination
timeFrame: Day 28
measure: Plasma iron concentration (µg/mL) at study end
timeFrame: Day 56
measure: Total iron binding capacity at baseline
timeFrame: Day 1
measure: Total iron binding capacity at time of vaccination
timeFrame: Day 28
measure: Total iron binding capacity at study end
timeFrame: Day 56
measure: Transferrin saturation (%) at baseline
timeFrame: Day 1
measure: Transferrin saturation (%) at time of vaccination
timeFrame: Day 28
measure: Transferrin saturation (%) at study end
timeFrame: Day 56
measure: Plasma ferritin concentration (µg/L) at baseline
timeFrame: Day 1
measure: Plasma ferritin concentration (µg/L) at time of vaccination
timeFrame: Day 28
measure: Plasma ferritin concentration (µg/L) at study end
timeFrame: Day 56
measure: Soluble transferrin receptor concentration (mg/L) at baseline
timeFrame: Day 1
measure: Soluble transferrin receptor concentration (mg/L) at time of vaccination
timeFrame: Day 28
measure: Soluble transferrin receptor concentration (mg/L) at study end
timeFrame: Day 56
measure: C-reactive protein concentration (mg/L) at baseline
timeFrame: Day 1
measure: C-reactive protein concentration (mg/L) at time of vaccination
timeFrame: Day 28
measure: C-reactive protein concentration (mg/L) at study end
timeFrame: Day 56
measure: Retinol binding protein concentration (µmol/L) at baseline
timeFrame: Day 1
measure: Retinol binding protein concentration (µmol/L) at time of vaccination
timeFrame: Day 28
measure: Retinol binding protein concentration (µmol/L) at study end
timeFrame: Day 56
measure: Alpha-glycoprotein (AGP) concentration at baseline
timeFrame: Day 1
measure: Alpha-glycoprotein concentration (g/L) at time of vaccination
timeFrame: Day 28
measure: Alpha-glycoprotein concentration (g/L) at study end
timeFrame: Day 56
measure: 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
timeFrame: Day 56
measure: COVID-19 specific T cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying specific cytokines' concentration.
timeFrame: Day 56
measure: Typhim Vi specific B-cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying antibodies' and memory B cell concentration.
timeFrame: Day 56
Other outcomes:
Locations:
city: Msambweni
country: Kenya
facility: Msambweni County Referral Hospital
Study officials:
affiliation: JKUAT
name: Simon Karanja, PhD
role: PRINCIPAL_INVESTIGATOR
References: