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

Iron Deficiency Anemia Clinical Trial

— DIVA_II  

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: NCT06116669
• Other study ID #: DIVA_II
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: Swiss Federal Institute of Technology
• Contact: Giulia Pironaci, MSc
• Phone: +41 44 632 93 29
• Email: giulia.pironaci[@]hest.ethz.ch
• 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: December 31, 2024
• Est. primary completion date: December 31, 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 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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron Deficiency Anemia

Intervention

Dietary Supplement:
• Iron supplementation
Iron supplements as 100 mg oral iron as FeSO4 given daily

Biological:
• MenACWY vaccine
MenACWY vaccination given on day 28 to all participants
• COVID-19 vaccine
Johnson & Johnson COVID- 19 (JJ COVID-19) vaccination given on day 28 to all participants

Other:
• Placebo
matching placebo capsules given daily

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

Locations

Country	Name	City	State
Kenya	Jomo Kenyatta University Of Agriculture And Technology	Nairobi

Sponsors (3)

Lead Sponsor	Collaborator
Swiss Federal Institute of Technology	Jomo Kenyatta University of Agriculture and Technology, University of Oxford

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	JJ COVID-19 vaccine response	Anti-spike (S1) IgG and anti-receptor-binding domain (RBD) IgG against SARS-COV-2	Day 56
Primary	MenACWY vaccine response	Measurement of antibody response against serogroups A, C, W, and Y.	Day 56
Primary	Typhoid vaccine response	Measurement of antibody response against Typhoid	Day 56
Secondary	Hemoglobin	iron status	Day 1
Secondary	Hemoglobin	iron status	Day 28
Secondary	Hemoglobin	iron status	Day 56
Secondary	Serum ferritin	iron status	Day 1
Secondary	Serum ferritin	iron status	Day 28
Secondary	Serum ferritin	iron status	Day 56
Secondary	soluble transferrin receptor	iron status	Day 1
Secondary	soluble transferrin receptor	iron status	Day 28
Secondary	soluble transferrin receptor	iron status	Day 56
Secondary	Plasma iron	iron status	Day 1
Secondary	Plasma iron	iron status	Day 28
Secondary	Plasma iron	iron status	Day 56
Secondary	Total iron binding capacity	iron status	Day 1
Secondary	Total iron binding capacity	iron status	Day 28
Secondary	Total iron binding capacity	iron status	Day 56
Secondary	Transferrin saturation	iron status	Day 1
Secondary	Transferrin saturation	iron status	Day 28
Secondary	Transferrin saturation	iron status	Day 56
Secondary	C- reactive protein	inflammation status	Day 1
Secondary	C- reactive protein	inflammation status	Day 28
Secondary	C- reactive protein	inflammation status	Day 56
Secondary	alpha- 1- glycoprotein	inflammation status	Day 1
Secondary	alpha- 1- glycoprotein	inflammation status	Day 28
Secondary	alpha- 1- glycoprotein	inflammation status	Day 56
Secondary	Retinol binding protein	Vitamin A status	Day 1
Secondary	Retinol binding protein	Vitamin A status	Day 28
Secondary	Retinol binding protein	Vitamin A status	Day 56
Secondary	Plasma zinc	Zinc status	Day 1
Secondary	COVID-19 specific T cell response	QuantiFERON SARS-CoV-2 whole blood assay - detection of IFN-gamma	Day 28
Secondary	COVID-19 specific T cell response	QuantiFERON SARS-CoV-2 whole blood assay - detection of IFN-gamma	Day 56
Secondary	COVID-19 specific T cell response	ELISpot assay on isolated peripheral blood mononuclear cells	Day 28
Secondary	COVID-19 specific T cell response	ELISpot assay on isolated peripheral blood mononuclear cells	Day 56
Secondary	Typhim Vi specific B-cell response	ELISpot assay on isolated peripheral blood mononuclear cells	Day 28
Secondary	Typhim Vi specific B-cell response	ELISpot assay on isolated peripheral blood mononuclear cells	Day 56