Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity
1 other identifier
interventional
150
1 country
1
Brief Summary
Iron deficiency (ID) anaemia (IDA) is a global public health problem, with the highest prevalence in Africa and in South-East Asia. While immunization programs have achieved high global coverage, vaccines often underperform in low- and middle-income countries (LMIC). The cause remains uncertain, but undernutrition, including ID, likely plays a role. Our recent in vitro and in vivo studies have shown the importance of iron status in adaptive immunity and vaccine response. Hypoferremia blunted T cell, B cell, and neutralizing antibody responses to influenza virus infection in mice, allowing the virus to persist. Iron deficient anaemic Kenyan women receiving intravenous iron at time of vaccination had a better immune response to the first dose of the ChAdOx Coronavirus 19 (COVID-19) vaccine and yellow fever vaccine. Japanese encephalitis and typhoid fever are endemic in Thailand. Vaccines are available but show variable efficacy. Whether ID impairs adult vaccine response to the live attenuated Japanese encephalitis (JE) and the Typhoid Vi polysaccharide (Vi-PS) vaccine and whether iron repletion via iron fortification improves vaccine response is uncertain. The objective of this study is to assess whether IDA in Thai women impairs immune response to the JE and the Typhoid Vi-PS vaccine and whether fortification iron improves their response. In this double-blind randomized controlled trial, IDA women will be assigned to two study groups: group 1 (fortification group) will receive iron-fortified biscuits (15mg iron as ferrous fumarate) for 56 days; group 2 (control group) will receive non-fortified biscuits for 56 days. All women will receive live attenuated JE and Typhoid Vi-PS vaccine on study day 28. Vaccine response will be measured 28 days after vaccination (on day 56) in both groups.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Sep 2023
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 30, 2023
CompletedStudy Start
First participant enrolled
September 6, 2023
CompletedFirst Posted
Study publicly available on registry
September 7, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 30, 2024
CompletedNovember 29, 2023
August 1, 2023
1.1 years
August 30, 2023
November 28, 2023
Conditions
Outcome Measures
Primary Outcomes (6)
Immunoglobulin G (IgG) concentrations against Salmonella Typhi
day 28 (time of vaccination)
Immunoglobulin A (IgA) concentrations against Salmonella Typhi
day 28 (time of vaccination)
Immunoglobulin G (IgG) concentrations against Salmonella Typhi
day 56 (4 weeks after vaccination)
Immunoglobulin A (IgA) concentrations against Salmonella Typhi
day 56 (4 weeks after vaccination)
Neutralizing antibodies against Japanese encephalitis
day 28 (time of vaccination)
Neutralizing antibodies against Japanese encephalitis
day 56 (4 weeks after vaccination)
Secondary Outcomes (30)
Hemoglobin concentration (g/dL)
day 0
Hemoglobin concentration (g/dL)
day 28
Hemoglobin concentration (g/dL)
day 56
zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
day 0
zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
day 28
- +25 more secondary outcomes
Study Arms (2)
Iron fortification group
EXPERIMENTALParticipants assigned to this group will receive iron-fortified cookies daily for the whole study duration
Control group
PLACEBO COMPARATORParticipants assigned to this group will receive the same cookies containing no iron daily for the whole study duration
Interventions
Study cookies fortified with ferrous fumarate, providing 15 mg of elemental iron in each portion.
All participants will be administered the live attenuated JE vaccine
All participants will be administered the typhoid Vi-PS vaccine
Eligibility Criteria
You may qualify if:
- Participant is willing and able to give informed consent for participation in the trial.
- Female aged 18-49 years.
- Diagnosed with anaemia (i.e. hemoglobin (Hb) concentration \<12 g/dl), but no severe anaemia (Hb \<8 g/dl), and iron deficiency (ZnPP \>40 µmol/mol)
- Anticipated residence in the area for the study duration
You may not qualify if:
- Pregnant (confirmed by rapid test during screening and at time of vaccination), lactating or planning pregnancy during the trial.
- Blood transfusion or intravenous iron treatment within 4 months of study start
- Major chronic infectious disease (e.g., tuberculosis, HIV+, hepatitis)
- Major chronic non-infectious disease (e.g., Type 1 or 2 diabetes, cancer)
- Treatment with supplemental iron two weeks prior to enrolment
- JE or typhoid vaccine within the past two years
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Oxfordlead
- Mahidol Universitycollaborator
- Ministry of Health, Thailandcollaborator
Study Sites (1)
Mahidol University
Roi Et, Thailand
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 30, 2023
First Posted
September 7, 2023
Study Start
September 6, 2023
Primary Completion
September 30, 2024
Study Completion
December 30, 2024
Last Updated
November 29, 2023
Record last verified: 2023-08
Data Sharing
- IPD Sharing
- Will not share