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

Not Applicable
Recruiting
Conditions
Iron Deficiency Anemia
Interventions
Dietary Supplement: Iron supplementation
Biological: MenACWY vaccine
Biological: COVID-19 vaccine
Other: Placebo
Biological: Typhim Vi vaccine
Registration Number
NCT06116669
Lead Sponsor
Swiss Federal Institute of Technology
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
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 infecious disease (e.g., HIV infection);
  • Major chronic non-infecious 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
  • Typhim Vi vaccine in the past
  • Pregnant (confirmed by rapid test during screening)
  • Malaria (confirmed by rapid test) à study start will be postponed

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control groupIron supplementationParticipants assigned to this group will receive placebo daily on study days 1-56.
Control groupPlaceboParticipants assigned to this group will receive placebo daily on study days 1-56.
Control groupTyphim Vi vaccineParticipants assigned to this group will receive placebo daily on study days 1-56.
Pre-treatment groupIron supplementationParticipants assigned to this group will receive 100 mg oral iron daily on study days 1-56.
Pre-treatment groupTyphim Vi vaccineParticipants assigned to this group will receive 100 mg oral iron daily on study days 1-56.
Simultaneous treatment groupCOVID-19 vaccineParticipants assigned to this group will receive placebo daily on study days 1-28 and 100 mg oral iron daily on study days 29-56.
Simultaneous treatment groupTyphim Vi vaccineParticipants assigned to this group will receive placebo daily on study days 1-28 and 100 mg oral iron daily on study days 29-56.
Control groupMenACWY vaccineParticipants assigned to this group will receive placebo daily on study days 1-56.
Control groupCOVID-19 vaccineParticipants assigned to this group will receive placebo daily on study days 1-56.
Pre-treatment groupCOVID-19 vaccineParticipants assigned to this group will receive 100 mg oral iron daily on study days 1-56.
Simultaneous treatment groupMenACWY vaccineParticipants assigned to this group will receive placebo daily on study days 1-28 and 100 mg oral iron daily on study days 29-56.
Pre-treatment groupMenACWY vaccineParticipants assigned to this group will receive 100 mg oral iron daily on study days 1-56.
Simultaneous treatment groupIron supplementationParticipants assigned to this group will receive placebo daily on study days 1-28 and 100 mg oral iron daily on study days 29-56.
Simultaneous treatment groupPlaceboParticipants assigned to this group will receive placebo daily on study days 1-28 and 100 mg oral iron daily on study days 29-56.
Primary Outcome Measures
NameTimeMethod
JJ COVID-19 vaccine responseDay 56

Anti-spike (S1) IgG and anti-receptor-binding domain (RBD) IgG against SARS-COV-2

MenACWY vaccine responseDay 56

Measurement of antibody response against serogroups A, C, W, and Y.

Typhoid vaccine responseDay 56

Measurement of antibody response against Typhoid

Secondary Outcome Measures
NameTimeMethod
HemoglobinDay 56

iron status

Serum ferritinDay 56

iron status

soluble transferrin receptorDay 56

iron status

alpha- 1- glycoproteinDay 56

inflammation status

Typhim Vi specific B-cell responseDay 56

ELISpot assay on isolated peripheral blood mononuclear cells

Plasma ironDay 56

iron status

Retinol binding proteinDay 56

Vitamin A status

Total iron binding capacityDay 56

iron status

Transferrin saturationDay 56

iron status

C- reactive proteinDay 56

inflammation status

Plasma zincDay 1

Zinc status

COVID-19 specific T cell responseDay 56

ELISpot assay on isolated peripheral blood mononuclear cells

Trial Locations

Locations (1)

Jomo Kenyatta University Of Agriculture And Technology

🇰🇪

Nairobi, Kenya

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