Clinical trial NCT06116669: Effects of Oral Iron Supplementation Before vs at Time of Vaccination on Immune 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
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: Jomo Kenyatta University of Agriculture and Technology
name: University of Oxford
First posted: 2023-11-03
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: OTHER

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 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

Primary outcomes:
measure: JJ COVID-19 vaccine response
timeFrame: Day 56
measure: MenACWY vaccine response
timeFrame: Day 56
measure: Typhoid vaccine response
timeFrame: Day 56
Secondary outcomes:
measure: Hemoglobin
timeFrame: Day 1
measure: Hemoglobin
timeFrame: Day 28
measure: Hemoglobin
timeFrame: Day 56
measure: Serum ferritin
timeFrame: Day 1
measure: Serum ferritin
timeFrame: Day 28
measure: Serum ferritin
timeFrame: Day 56
measure: soluble transferrin receptor
timeFrame: Day 1
measure: soluble transferrin receptor
timeFrame: Day 28
measure: soluble transferrin receptor
timeFrame: Day 56
measure: Plasma iron
timeFrame: Day 1
measure: Plasma iron
timeFrame: Day 28
measure: Plasma iron
timeFrame: Day 56
measure: Total iron binding capacity
timeFrame: Day 1
measure: Total iron binding capacity
timeFrame: Day 28
measure: Total iron binding capacity
timeFrame: Day 56
measure: Transferrin saturation
timeFrame: Day 1
measure: Transferrin saturation
timeFrame: Day 28
measure: Transferrin saturation
timeFrame: Day 56
measure: C- reactive protein
timeFrame: Day 1
measure: C- reactive protein
timeFrame: Day 28
measure: C- reactive protein
timeFrame: Day 56
measure: alpha- 1- glycoprotein
timeFrame: Day 1
measure: alpha- 1- glycoprotein
timeFrame: Day 28
measure: alpha- 1- glycoprotein
timeFrame: Day 56
measure: Retinol binding protein
timeFrame: Day 1
measure: Retinol binding protein
timeFrame: Day 28
measure: Retinol binding protein
timeFrame: Day 56
measure: Plasma zinc
timeFrame: Day 1
measure: COVID-19 specific T cell response
timeFrame: Day 28
measure: COVID-19 specific T cell response
timeFrame: Day 56
measure: COVID-19 specific T cell response
timeFrame: Day 28
measure: COVID-19 specific T cell response
timeFrame: Day 56
measure: Typhim Vi specific B-cell response
timeFrame: Day 28
measure: Typhim Vi specific B-cell response
timeFrame: Day 56
Other outcomes:
Locations:
city: Nairobi
country: Kenya
facility: Jomo Kenyatta University Of Agriculture And Technology
Study officials:
References: