Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity

Iron Deficiency Anemia Clinical Trial

Official title:

Iron Fortified Food to Improve Japanese Encephalitis and Typhoid Fever Vaccine Immunogenicity: a Randomized Controlled Trial in Iron Deficient Thai Women

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06027801
• Other study ID #: VEST
• Status: Recruiting
• Phase: N/A
• Start date: September 6, 2023
• Est. completion date: December 30, 2024

Study information

• Verified date: August 2023
• Source: University of Oxford
• Contact: Nicole Stoffel, PhD
• Phone: 044 632 83 93
• Email: nicole.stoffel[@]rdm.ox.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Encephalitis
• Encephalitis, Japanese
• Iron Deficiency Anemia
• Typhoid Fever

Intervention

Other:
• Iron-fortified cookies
Study cookies fortified with ferrous fumarate, providing 15 mg of elemental iron in each portion.

Biological:
• Japanese encephalitis (JE) vaccine
All participants will be administered the live attenuated JE vaccine
• Typhoid Vi polysaccharide (Vi-PS) vaccine
All participants will be administered the typhoid Vi-PS vaccine

Other:
• non-fortified cookies
Study cookies containing no iron

Locations

Country	Name	City	State
Thailand	Mahidol University	Roi Et

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	Mahidol University, Ministry of Health, Thailand

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunoglobulin G (IgG) concentrations against Salmonella Typhi		day 28 (time of vaccination)
Primary	Immunoglobulin A (IgA) concentrations against Salmonella Typhi		day 28 (time of vaccination)
Primary	Immunoglobulin G (IgG) concentrations against Salmonella Typhi		day 56 (4 weeks after vaccination)
Primary	Immunoglobulin A (IgA) concentrations against Salmonella Typhi		day 56 (4 weeks after vaccination)
Primary	Neutralizing antibodies against Japanese encephalitis		day 28 (time of vaccination)
Primary	Neutralizing antibodies against Japanese encephalitis		day 56 (4 weeks after vaccination)
Secondary	Hemoglobin concentration (g/dL)		day 0
Secondary	Hemoglobin concentration (g/dL)		day 28
Secondary	Hemoglobin concentration (g/dL)		day 56
Secondary	zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)		day 0
Secondary	zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)		day 28
Secondary	zinc protoporphyrin (ZnPP) concentration (µmol/mol heme)		day 56
Secondary	serum iron (SFe) concentration (ng/µl)		day 0
Secondary	serum iron (SFe) concentration (ng/µl)		day 28
Secondary	serum iron (SFe) concentration (ng/µl)		day 56
Secondary	total iron binding capacity (µg/dL)		day 0
Secondary	total iron binding capacity (µg/dL)		day 28
Secondary	total iron binding capacity (µg/dL)		day 56
Secondary	transferrin saturation (TSAT) (%)		day 0
Secondary	transferrin saturation (TSAT) (%)		day 28
Secondary	transferrin saturation (TSAT) (%)		day 56
Secondary	plasma ferritin (PF) concentration (µg/L)		day 0
Secondary	plasma ferritin (PF) concentration (µg/L)		day 28
Secondary	plasma ferritin (PF) concentration (µg/L)		day 56
Secondary	soluble transferrin receptor (sTfR) concentration (mg/L)		day 0
Secondary	soluble transferrin receptor (sTfR) concentration (mg/L)		day 28
Secondary	soluble transferrin receptor (sTfR) concentration (mg/L)		day 56
Secondary	C-reactive protein (CRP) concentration (mg/L)		day 0
Secondary	C-reactive protein (CRP) concentration (mg/L)		day 28
Secondary	C-reactive protein (CRP) concentration (mg/L)		day 56
Secondary	alpha-glycoprotein (AGP) concentration (g/L)		day 0
Secondary	alpha-glycoprotein (AGP) concentration (g/L)		day 28
Secondary	alpha-glycoprotein (AGP) concentration (g/L)		day 56
Secondary	retinol-binding protein concentration (µmol/L)		day 0
Secondary	retinol-binding protein concentration (µmol/L)		day 28
Secondary	retinol-binding protein concentration (µmol/L)		day 56