Iron and Immune Response to Vaccine (IRONMUM)

NCT05385042 | Completed

• 1 other identifier: HCR22001
• Study Type: interventional
• Target: 171
• Locations: 1 country
• Sites: 1

Brief Summary

Iron deficiency causes anaemia and is common in pregnant women especially for those living in tropical regions where a high burden of infection and poor nutrition can compromise health. Low iron has been recognized as a cause of poor immune response because the group of cells that need to increase to make the immune response need iron to function. Vaccination is an important part of care during pregnancy because components of the immune response can cross the placenta and protect the young infant. More recently COVID-19 vaccination has also been recommended for pregnant women due to their higher risk of dying from this infection. Deeper investigation of whether low iron results in poor immune response is needed because the vaccines may not be providing as much protection as needed. The World Health Organization also recommends nutritional iron supplements in pregnancy and whether these improve immune response to vaccines is also not known. This study aims to test the body's immune response to recommended vaccines in pregnant women (tetanus and diphtheria (combination) and COVID-19 vaccine (if indicated)) who are anaemic and receiving iron supplements and compare their response to women who are not anaemic, who only receive a preventive, lower dose of supplement.

Conditions

Pregnancy Related

Keywords

Iron supplementation; Immune responses; Maternal vaccination

Outcome Measures

Primary Outcomes (1)

• Antibody responses to maternal vaccine

  Antibody responses to diphtheria-tetanus and SARS-CoV-2 immunisation, measured by ELISA.

  change from baseline before immunisation and at 7-days and 28-days after immunisation, and at 2 months post-partum in mother and infant.

Secondary Outcomes (6)

• Cellular Immune response post-immunisation measured by Mass Cytometry (plasma cells and circulating T-follicular helper cells).

  7-days after immunisation

• Profile of the circulating immune system components over the course of pregnancy measured by CyTOF

  change from before immunisation, 7-days and 28-days after immunization and until 2 months post-partum in mother and infant

• Haematological, iron and inflammatory parameters including: Hb, MCV, haematocrit serum iron, ferritin, TSAT, hepcidin, CRP, G6PD, Hb typing.

  change from before immunisation, 7-days and 28-days after immunization and at 2 months post-partum in mother and infant

• Haematocrit from baseline if anaemic at baseline according to trimester of gestation

  change from baseline and month 1,2 and 3, and delivery

• Modified Adherence Starts with Knowledge (ASK-12) questionnaire including pill count.

  Month 1,2 and 3

Other Outcomes (1)

• To assess if the amount of betel nut consumption relates to Haematocrit response

  change from baseline and month 1,2 and 3

Study Arms (2)

Non-anaemic pregnant women

OTHER

50 pregnant women who have normal haematocrit (not anaemic) at 12 weeks.

Dietary Supplement: Sangobion and Thiamine Hydrochloride

Anaemic pregnant women

OTHER

100 pregnant women who have haematocrit below 33% (equates to Hb 11g/dL) in first trimester (\<14 weeks gestation) and below 30% (equates to Hb 10g/dL).

Dietary Supplement: Sangobion, Thiamine hydrochloride and Vitamin B12

Interventions

Sangobion and Thiamine Hydrochloride DIETARY_SUPPLEMENT

Prophylactic dietary supplements: 1 capsule of Sangobion + separate Thiamine Hydrochloride tablet 100mg per day for 12 weeks. Then non-anaemic pregnant women will continue with prophylactic nutritional supplements until delivery.

Non-anaemic pregnant women

Sangobion, Thiamine hydrochloride and Vitamin B12 DIETARY_SUPPLEMENT

Treatment dietary supplements: 3 capsules of Sangobion + separate Thiamine Hydrochloride tablet 100mg, Vit B12 100mcg per day for 12 weeks. If experience a therapeutic increase of 3% Haematocrit within 28 days (responders), they will continue with prophylactic nutritional supplements until delivery. If no affect in Haematocrit level within 28 days (non-responders; defined by trimester of diagnosis), they will be investigated for their serum ferritin and if this is low (\<15ng/mL) intravenous (iv) iron supplement (Venofer®) will be provided. The dose will be calculated for the individual concerned (required iron dose (mg) = (2.4 x (target Hb of 11g/dL (Ht 33%) x pre-pregnancy weight (kg) +1000mg for replenishment of stores). Doses will be administered by slow iv infusion 200 mg per dose (maximum of 3 doses per week). Following treatment they will continue with prophylactic nutritional supplements.

Anaemic pregnant women

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Pregnant women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Viable singleton pregnancy\<28 weeks confirmed by ultrasound
• years and older
• Willingness and ability to comply with the study protocol for the duration of the study
• Can understand information about the study and provide consent

You may not qualify if:

• Any diphtheria-tetanus vaccine within the previous 2 years
• History of allergic reaction to diphtheria-tetanus or COVID-19 vaccine
• Haematocrit \<21% or Haematocrit \>50%
• Known severe haemoglobinopathy (HbE/beta-thalassaemia syndrome, beta-thalassaemia major or HbH syndrome)\* or G6PD deficiency
• \* Iron supplementation is safe in pregnant women with haemoglobin E, alpha-thalassemia 1, or beta-thalassemia carriers.
• HIV-positive
• Slide confirmed presence of malaria
• Fever (defined at \>37.5°C)
• Symptoms of COVID (these women will be PCR tested as routine in clinic)
• Known severe medical or obstetric complication e.g. valvular heart disease, placenta praevia
• Known or clinical vitB12 deficiency as indicated by megaloblastic anaemia (pernicious anaemia or clinical symptoms)

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Shoklo Malaria Research Unit (SMRU)

Mae Sot, Changwat Tak, 63110, Thailand

Location

MeSH Terms

Interventions

thiamine hydrochloride; Vitamin B 12

Intervention Hierarchy (Ancestors)

Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Hal Drakesmith, Dr.

  MRC Human Immunology Unit, John Radcliffe Hospital, University of Oxford, OX3 9DS UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is a prospective open-label study in which both participants and investigators know the identity of the treatment and its dosage.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: May 23, 2022
• Study Start: June 18, 2022
• Primary Completion: July 22, 2025
• Study Completion: July 22, 2025
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: After completion of trial activities. PI will upload results within 12 months of the end of the trial declaration.
• Access Criteria: MORU Data Sharing Policy. The criteria for authorship will be consistent with the international guidelines (http://www.icmje.org/#author).

Locations

TH (1)