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

Federal Institute of Technology (ETH) Zurich

Status: Enrolling

Conditions: Iron Deficiency Anemia

Treatments: Other: Placebo; Biological: Typhim Vi vaccine; Biological: MenACWY vaccine; Dietary Supplement: Iron supplementation; Biological: COVID-19 vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT06116669

DIVA_II

Details and patient eligibility

About

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.

Enrollment: 180 estimated patients

Sex: Female

Ages: 18 to 49 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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180 participants in 3 patient groups, including a placebo group

Pre-treatment group

Experimental group

Description:

Participants assigned to this group will receive 100 mg oral iron daily on study days 1-56.

Treatment:

Dietary Supplement: Iron supplementation

Biological: COVID-19 vaccine

Biological: Typhim Vi vaccine

Biological: MenACWY vaccine

Simultaneous treatment group

Experimental group

Description:

Participants assigned to this group will receive placebo daily on study days 1-28 and 100 mg oral iron daily on study days 29-56.

Treatment:

Dietary Supplement: Iron supplementation

Biological: COVID-19 vaccine

Biological: Typhim Vi vaccine

Other: Placebo

Biological: MenACWY vaccine

Control group

Placebo Comparator group

Description:

Participants assigned to this group will receive placebo daily on study days 1-56.

Treatment:

Dietary Supplement: Iron supplementation

Biological: COVID-19 vaccine

Biological: Typhim Vi vaccine

Other: Placebo

Biological: MenACWY vaccine