Effects of Iron Supplementation on Pediatric Vaccine Response

Study Overview
=================
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.

Official Title
-----------------
Effects of Iron Supplementation on Pediatric Vaccine Response

Conditions
-----------------
Iron-deficiency, Iron Deficiency Anemia, Vaccination, Pediatric ALL

Intervention / Treatment
-----------------
* Dietary Supplement: Iron syrup
* Dietary Supplement: Multivitamin syrup


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 39 Days
Maximum Age: 45 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate iron treatment<br>Iron and multivitamin syrup | Dietary Supplement: Iron syrup<br>* Daily supplementation with iron<br>Dietary Supplement: Multivitamin syrup<br>* Daily supplementation with multivitamins<br>|
| Placebo Comparator: Delayed iron treatment<br>Multivitamin syrup | Dietary Supplement: Multivitamin syrup<br>* Daily supplementation with multivitamins<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion |  | 6 weeks of age | 
| Seroconversion |  | 14 weeks of age | 
| Seroconversion |  | 24 weeks of age | 
| Seroconversion |  | 38 weeks of age | 
| Seroconversion |  | 52 weeks of age | 
| Antibody titers |  | 6 weeks of age | 
| Antibody titers |  | 14 weeks of age | 
| Antibody titers |  | 24 weeks of age | 
| Antibody titers |  | 38 weeks of age | 
| Antibody titers |  | 52 weeks of age | 
| Antibody avidity index | percentage of antibodies that remain bound to beads | 6 weeks of age | 
| Antibody avidity index | percentage of antibodies that remain bound to beads | 14 weeks of age | 
| Antibody avidity index | percentage of antibodies that remain bound to beads | 24 weeks of age | 
| Antibody avidity index | percentage of antibodies that remain bound to beads | 38 weeks of age | 
| Antibody avidity index | percentage of antibodies that remain bound to beads | 52 weeks of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| antiviral immunoglobulin G response | Immunoassay | 6 weeks of age | 
| antiviral immunoglobulin G response | Immunoassay | 24 weeks of age | 
| infant antiviral immunoglobulin G response | Immunoassay | 52 weeks of age | 
| immune cell populations | number and type of immune cells | 6 weeks of age | 
| immune cell populations | number and type of immune cells | 24 weeks of age | 
| immune cell populations | number and type of immune cells | 52 weeks of age | 
| Proteomics | Proteins involved in immune response | 6 weeks of age | 
| Proteomics | Proteins involved in immune response | 24 weeks of age | 
| Proteomics | Proteins involved in immune response | 52 weeks of age | 
| Transcriptomics | Genes involved in immune response | 24 weeks of age | 
| Human milk oligosaccharide secretor type | secretor yes or no | 14 weeks of age | 
| Intestinal fatty acid binding protein | Gut inflammation | 6 weeks of age | 
| Intestinal fatty acid binding protein | Gut inflammation | 14 weeks of age | 
| Intestinal fatty acid binding protein | Gut inflammation | 24 weeks of age | 
| Calprotectin | Gut inflammation | 6 weeks of age | 
| Calprotectin | Gut inflammation | 14 weeks of age | 
| Calprotectin | Gut inflammation | 24 weeks of age | 
| Hemoglobin |  | 6 weeks of age | 
| Hemoglobin |  | 14 weeks of age | 
| Hemoglobin |  | 24 weeks of age | 
| Hemoglobin |  | 38 weeks of age | 
| Hemoglobin |  | 52 weeks of age | 
| Erythrocyte zinc protoporphyrin |  | 6 weeks of age | 
| Erythrocyte zinc protoporphyrin |  | 14 weeks of age | 
| Erythrocyte zinc protoporphyrin |  | 24 weeks of age | 
| Erythrocyte zinc protoporphyrin |  | 38 weeks of age | 
| Erythrocyte zinc protoporphyrin |  | 52 weeks of age | 
| Serum iron |  | 6 weeks of age | 
| Serum iron |  | 14 weeks of age | 
| Serum iron |  | 24 weeks of age | 
| Serum iron |  | 38 weeks of age | 
| Serum iron |  | 52 weeks of age | 
| Plasma ferritin |  | 6 weeks of age | 
| Plasma ferritin |  | 14 weeks of age | 
| Plasma ferritin |  | 24 weeks of age | 
| Plasma ferritin |  | 38 weeks of age | 
| Plasma ferritin |  | 52 weeks of age | 
| Transferrin receptor |  | 6 weeks of age | 
| Transferrin receptor |  | 14 weeks of age | 
| Transferrin receptor |  | 24 weeks of age | 
| Transferrin receptor |  | 38 weeks of age | 
| Transferrin receptor |  | 52 weeks of age | 
| C-reactive protein |  | 6 weeks of age | 
| C-reactive protein |  | 14 weeks of age | 
| C-reactive protein |  | 24 weeks of age | 
| C-reactive protein |  | 38 weeks of age | 
| C-reactive protein |  | 52 weeks of age | 
| Alpha-glycoprotein |  | 6 weeks of age | 
| Alpha-glycoprotein |  | 14 weeks of age | 
| Alpha-glycoprotein |  | 24 weeks of age | 
| Alpha-glycoprotein |  | 38 weeks of age | 
| Alpha-glycoprotein |  | 52 weeks of age | 
| Intestinal fatty acid binding protein |  | 6 weeks of age | 
| Intestinal fatty acid binding protein |  | 14 weeks of age | 
| Intestinal fatty acid binding protein |  | 24 weeks of age | 
| Intestinal fatty acid binding protein |  | 38 weeks of age | 
| Intestinal fatty acid binding protein |  | 52 weeks of age |