Effects of Oral Iron Supplementation Before vs. at Time of Vaccination on Immune Response in Iron Deficient Kenyan Women
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Pre-treatment group
Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.
干预措施: Oral iron supplementation (pre-treatment) (Dietary Supplement)
Pre-treatment group
Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.
干预措施: COVID-19 vaccine (Biological)
Pre-treatment group
Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.
干预措施: MenACWY vaccine (Biological)
Pre-treatment group
Participants assigned to this group will receive 200 mg oral iron on alternate days on study days 1-56.
干预措施: Typhim Vi vaccine (Biological)
Simultaneous treatment group
Participants assigned to this group will receive placebo on alternate days on study days 1-28 and 200 mg oral iron on alternate days on study days 29-56.
干预措施: COVID-19 vaccine (Biological)
Simultaneous treatment group
Participants assigned to this group will receive placebo on alternate days on study days 1-28 and 200 mg oral iron on alternate days on study days 29-56.
干预措施: MenACWY vaccine (Biological)
Simultaneous treatment group
Participants assigned to this group will receive placebo on alternate days on study days 1-28 and 200 mg oral iron on alternate days on study days 29-56.
干预措施: Oral iron supplementation (simultaneous treatment) (Dietary Supplement)
Simultaneous treatment group
Participants assigned to this group will receive placebo on alternate days on study days 1-28 and 200 mg oral iron on alternate days on study days 29-56.
干预措施: Typhim Vi vaccine (Biological)
Control group
Participants assigned to this group will receive placebo on alternate days on study days 1-56.
干预措施: COVID-19 vaccine (Biological)
Control group
Participants assigned to this group will receive placebo on alternate days on study days 1-56.
干预措施: MenACWY vaccine (Biological)
Control group
Participants assigned to this group will receive placebo on alternate days on study days 1-56.
干预措施: Typhim Vi vaccine (Biological)
结局指标
主要结局
IgG concentration against meningococcal serogroups A, C, W, and Y (anti-MenACWY IgG) [iU/ml]
时间窗: Day 56
IgG concentration against Typhoid [iU/ml]
时间窗: Day 56
anti-spike (S1) immunoglobulin (IgG) and anti-receptor-binding domain (RBD) IgG concentrations against severe acute respiratory syndrome (SARS)-Coronavirus (COV)-2 [iU/ml]
时间窗: Day 56
次要结局
- Hemoglobin concentration (g/L) at study end(Days 56)
- Zinc protoporphyrin concentration (µmol/mol heme) at study end(Day 56)
- Plasma iron concentration (µg/mL) at time of vaccination(Day 28)
- Plasma iron concentration (µg/mL) at study end(Day 56)
- Total iron binding capacity at study end(Day 56)
- Transferrin saturation (%) at baseline(Day 1)
- Hemoglobin concentration (g/L) at baseline(Day 1)
- Hemoglobin concentration (g/L) at time of vaccination(Day 28)
- Total iron binding capacity at baseline(Day 1)
- Total iron binding capacity at time of vaccination(Day 28)
- C-reactive protein concentration (mg/L) at time of vaccination(Day 28)
- Retinol binding protein concentration (µmol/L) at baseline(Day 1)
- Zinc protoporphyrin concentration (µmol/mol heme) at time of vaccination(Day 28)
- Plasma iron concentration (µg/mL) at baseline(Day 1)
- Plasma ferritin concentration (µg/L) at study end(Day 56)
- Retinol binding protein concentration (µmol/L) at study end(Day 56)
- Zinc protoporphyrin concentration (µmol/mol heme) at baseline(Day 1)
- Soluble transferrin receptor concentration (mg/L) at time of vaccination(Day 28)
- C-reactive protein concentration (mg/L) at baseline(Day 1)
- C-reactive protein concentration (mg/L) at study end(Day 56)
- Alpha-glycoprotein concentration (g/L) at study end(Day 56)
- 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(Day 56)
- COVID-19 specific T cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying specific cytokines' concentration.(Day 56)
- Transferrin saturation (%) at time of vaccination(Day 28)
- Transferrin saturation (%) at study end(Day 56)
- Plasma ferritin concentration (µg/L) at baseline(Day 1)
- Plasma ferritin concentration (µg/L) at time of vaccination(Day 28)
- Soluble transferrin receptor concentration (mg/L) at baseline(Day 1)
- Retinol binding protein concentration (µmol/L) at time of vaccination(Day 28)
- Alpha-glycoprotein (AGP) concentration at baseline(Day 1)
- Typhim Vi specific B-cell response measured in peripheral blood mononuclear cells by ELISpot assay quantifying antibodies' and memory B cell concentration.(Day 56)
- Alpha-glycoprotein concentration (g/L) at time of vaccination(Day 28)
- Soluble transferrin receptor concentration (mg/L) at study end(Day 56)
研究者
Nicole Stoffel
Prof. Dr.
ETH Zurich