Clinical trial NCT04744818: Effects of Iron Supplementation on Pediatric Vaccine Response
Official title: Effects of Iron Supplementation on Pediatric Vaccine Response
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Iron-deficiency
Iron Deficiency Anemia
Vaccination
Pediatric ALL
Lead sponsor: Swiss Federal Institute of Technology
Sponsor class: OTHER
Collaborators: name: Jomo Kenyatta University of Agriculture and Technology Kenya
name: Karolinka Institute Sweden
name: University of Oxford
name: National Institute for Public Health and Environment Netherlands
First posted: 2021-02-09
Enrollment: 288
Sex: ALL
Minimum age (years): 39
Maximum age (years): 45
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: ID/IDA affects many young children in Africa. Vaccines provide tremendous benefits in LMIC; however, they currently fail to reach their full potential. We need to better understand the causes of vaccine failure, in order to develop new strategies to improve vaccine immunogenicity.

This study will contribute to children's health by: (1) providing updated guidelines to better define the prevalence of ID/IDA in early infancy, and its safe and effective control using iron; and (2) providing a new approach to improve response to pediatric vaccines in LMIC, by ensuring adequate iron status at time of vaccination.

Detailed description: Two major pediatric public health goals in LMIC are increasing immunization effectiveness and reducing ID/IDA in children. ID/IDA affects many young children in Africa. Current guidelines do not recommend routine testing of hemoglobin in early infancy, as it is generally believed that most infants are born with adequate iron stores to last 6 months. However, many African infants are born with low iron stores and ID/IDA may develop earlier than generally appreciated, within 2-3 months after birth. Vaccines provide tremendous benefits in LMIC; however, they currently fail to reach their full potential. We need to better understand the causes of vaccine failure, in order to develop new strategies to improve vaccine immunogenicity. Despite lower efficacy in LMIC, these vaccines provide a major benefit because the disease burden is so high; however, if approaches can be found to improve immunogenicity, these vaccines would be even more powerful.

For this study, 6 weeks old infants will be randomly assigned to two study groups. Group 1 will receive iron at time of pediatric vaccinations from age 6-24 weeks. Group 2 will receive no iron at time of pediatric vaccinations. All infants will receive a multivitamin syrup from age 6-24 weeks. All infants remaining ID/IDA at age 24 weeks will receive iron. Infants will be followed-up until age 52 weeks.

Eligibility criteria: Inclusion Criteria:

* Mother at least ≥15 years of age.
* 6 weeks (+/- 3 days) of age
* Iron deficient (erythrocyte zinc protoporphyrin (ZnPP) \>61 μmol/mol heme)
* With or without anemia, but not severely anemic (Hb \>70 g/L)
* No malaria
* No medical condition that precludes study involvement
* Mother HIV negative
* Vaginal delivery
* No iron supplementation prior to study enrolment
* Not wasted (length for height z score of ≥-2)
* Not underweight (weight for age z score ≥-2)
* From the hospital record, term or late preterm delivery (≥34 weeks)
* Full-time breastfed at least until the screening
* No vaccines beyond the birth dose of OPV and BCG prior to enrolment

Primary outcomes:
measure: Pertussis antibody profile
timeFrame: from 6 to 24 weeks
measure: Diphtheria antibody profile
timeFrame: from 6 to 24 weeks
Secondary outcomes:
measure: antiviral immunoglobulin G response
timeFrame: 6 weeks of age
measure: antiviral immunoglobulin G response
timeFrame: 24 weeks of age
measure: infant antiviral immunoglobulin G response
timeFrame: 52 weeks of age
measure: immune cell populations
timeFrame: 6 weeks of age
measure: immune cell populations
timeFrame: 24 weeks of age
measure: immune cell populations
timeFrame: 52 weeks of age
measure: Proteomics
timeFrame: 6 weeks of age
measure: Proteomics
timeFrame: 24 weeks of age
measure: Proteomics
timeFrame: 52 weeks of age
measure: Transcriptomics
timeFrame: 24 weeks of age
measure: Intestinal fatty acid binding protein
timeFrame: 6 weeks of age
measure: Intestinal fatty acid binding protein
timeFrame: 14 weeks of age
measure: Intestinal fatty acid binding protein
timeFrame: 24 weeks of age
measure: Calprotectin
timeFrame: 6 weeks of age
measure: Calprotectin
timeFrame: 14 weeks of age
measure: Calprotectin
timeFrame: 24 weeks of age
measure: Hemoglobin
timeFrame: 6 weeks of age
measure: Hemoglobin
timeFrame: 14 weeks of age
measure: Hemoglobin
timeFrame: 24 weeks of age
measure: Hemoglobin
timeFrame: 38 weeks of age
measure: Hemoglobin
timeFrame: 52 weeks of age
measure: Plasma iron
timeFrame: 6 weeks of age
measure: Plasma iron
timeFrame: 14 weeks of age
measure: Plasma iron
timeFrame: 24 weeks of age
measure: Plasma iron
timeFrame: 38 weeks of age
measure: Plasma iron
timeFrame: 52 weeks of age
measure: Plasma ferritin
timeFrame: 6 weeks of age
measure: Plasma ferritin
timeFrame: 14 weeks of age
measure: Plasma ferritin
timeFrame: 24 weeks of age
measure: Plasma ferritin
timeFrame: 38 weeks of age
measure: Plasma ferritin
timeFrame: 52 weeks of age
measure: soluble transferrin receptor
timeFrame: 6 weeks of age
measure: soluble transferrin receptor
timeFrame: 14 weeks of age
measure: soluble transferrin receptor
timeFrame: 24 weeks of age
measure: soluble transferrin receptor
timeFrame: 38 weeks of age
measure: soluble transferrin receptor
timeFrame: 52 weeks of age
measure: C-reactive protein
timeFrame: 6 weeks of age
measure: C-reactive protein
timeFrame: 14 weeks of age
measure: C-reactive protein
timeFrame: 24 weeks of age
measure: C-reactive protein
timeFrame: 38 weeks of age
measure: C-reactive protein
timeFrame: 52 weeks of age
measure: Alpha-glycoprotein
timeFrame: 6 weeks of age
measure: Alpha-glycoprotein
timeFrame: 14 weeks of age
measure: Alpha-glycoprotein
timeFrame: 24 weeks of age
measure: Alpha-glycoprotein
timeFrame: 38 weeks of age
measure: Alpha-glycoprotein
timeFrame: 52 weeks of age
measure: Tetanus antibody profile
timeFrame: from 6 to 24 weeks
measure: Haemophilus influenzae b antibody profile
timeFrame: from 6 to 24 weeks
measure: Pneumococcus antibody profile
timeFrame: from 6 to 24 weeks
measure: Rotavirus antibody profile
timeFrame: from 6 to 24 weeks
measure: Polio antibody profile
timeFrame: from 6 to 24 weeks
measure: Anti-vaccine antibody titers
timeFrame: 38 weeks of age
measure: Anti-vaccine antibody titers
timeFrame: 52 weeks of age
measure: Anti-vaccine seroconversion
timeFrame: 14 weeks of age
measure: Anti-vaccine seroconversion
timeFrame: 24 weeks of age
measure: Anti-vaccine seroconversion
timeFrame: 38 weeks of age
measure: Anti-vaccine seroconversion
timeFrame: 52 weeks of age
measure: Anti-vaccine antibody avidity index
timeFrame: 14 weeks of age
measure: Anti-vaccine antibody avidity index
timeFrame: 24 weeks of age
measure: Anti-vaccine antibody avidity index
timeFrame: 38 weeks of age
measure: Anti-vaccine antibody avidity index
timeFrame: 52 weeks of age
Other outcomes:
measure: Human milk oligosaccharide secretor type
timeFrame: 14 weeks of age
measure: Erythrocyte zinc protoporphyrin
timeFrame: 6 weeks of age
measure: Erythrocyte zinc protoporphyrin
timeFrame: 14 weeks of age
measure: Erythrocyte zinc protoporphyrin
timeFrame: 24 weeks of age
measure: Erythrocyte zinc protoporphyrin
timeFrame: 38 weeks of age
measure: Erythrocyte zinc protoporphyrin
timeFrame: 52 weeks of age
Locations:
city: Msambweni
country: Kenya
facility: Msambweni County Referral Hospital
state: Kwale
city: Zürich
country: Switzerland
facility: Human Nutrition Laboratory ETH Zurich
Study officials:
References: