Clinical trial NCT06027801: Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity
Official title: Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity: a Randomized Controlled Trial in Iron Deficient Thai Women
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Iron Deficiency Anemia
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Mahidol University
name: Ministry of Health, Thailand
First posted: 2023-09-07
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Immunoglobulin G (IgG) concentrations against Salmonella Typhi
timeFrame: day 28 (time of vaccination)
measure: Immunoglobulin A (IgA) concentrations against Salmonella Typhi
timeFrame: day 28 (time of vaccination)
measure: Immunoglobulin G (IgG) concentrations against Salmonella Typhi
timeFrame: day 56 (4 weeks after vaccination)
measure: Immunoglobulin A (IgA) concentrations against Salmonella Typhi
timeFrame: day 56 (4 weeks after vaccination)
measure: Neutralizing antibodies against Japanese encephalitis
timeFrame: day 28 (time of vaccination)
measure: Neutralizing antibodies against Japanese encephalitis
timeFrame: day 56 (4 weeks after vaccination)
Secondary outcomes:
measure: Hemoglobin concentration (g/dL)
timeFrame: day 0
measure: Hemoglobin concentration (g/dL)
timeFrame: day 28
measure: Hemoglobin concentration (g/dL)
timeFrame: day 56
measure: zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
timeFrame: day 0
measure: zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
timeFrame: day 28
measure: zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)
timeFrame: day 56
measure: serum iron (SFe) concentration (ng/µl)
timeFrame: day 0
measure: serum iron (SFe) concentration (ng/µl)
timeFrame: day 28
measure: serum iron (SFe) concentration (ng/µl)
timeFrame: day 56
measure: total iron binding capacity (µg/dL)
timeFrame: day 0
measure: total iron binding capacity (µg/dL)
timeFrame: day 28
measure: total iron binding capacity (µg/dL)
timeFrame: day 56
measure: transferrin saturation (TSAT) (%)
timeFrame: day 0
measure: transferrin saturation (TSAT) (%)
timeFrame: day 28
measure: transferrin saturation (TSAT) (%)
timeFrame: day 56
measure: plasma ferritin (PF) concentration (µg/L)
timeFrame: day 0
measure: plasma ferritin (PF) concentration (µg/L)
timeFrame: day 28
measure: plasma ferritin (PF) concentration (µg/L)
timeFrame: day 56
measure: soluble transferrin receptor (sTfR) concentration (mg/L)
timeFrame: day 0
measure: soluble transferrin receptor (sTfR) concentration (mg/L)
timeFrame: day 28
measure: soluble transferrin receptor (sTfR) concentration (mg/L)
timeFrame: day 56
measure: C-reactive protein (CRP) concentration (mg/L)
timeFrame: day 0
measure: C-reactive protein (CRP) concentration (mg/L)
timeFrame: day 28
measure: C-reactive protein (CRP) concentration (mg/L)
timeFrame: day 56
measure: alpha-glycoprotein (AGP) concentration (g/L)
timeFrame: day 0
measure: alpha-glycoprotein (AGP) concentration (g/L)
timeFrame: day 28
measure: alpha-glycoprotein (AGP) concentration (g/L)
timeFrame: day 56
measure: retinol-binding protein concentration (µmol/L)
timeFrame: day 0
measure: retinol-binding protein concentration (µmol/L)
timeFrame: day 28
measure: retinol-binding protein concentration (µmol/L)
timeFrame: day 56
Other outcomes:
Locations:
city: Roi Et
country: Thailand
facility: Mahidol University
Study officials:
References: