Trial of Antibody Responses by Vitamin Supplementation

Study Overview
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Brief Summary
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Streptococcus pneumoniae, commonly called pneumococcus, can cause a wide range of diseases in children from mild ear infections to deadly pneumonia or meningitis. Vaccination is currently the single best way to protect children. Nutrition, especially the amount of vitamin A, may play a role in how well your body responds to infection or a vaccine. We call this an immune response. This research will look to see if children who take a vitamin with their vaccine have a better immune response than children who do not take a vitamin with their vaccine. Primary Objective To evaluate the influence of vitamin A supplementation on Prevnar vaccine immunogenicity based on changes in antibody scores in a commercial ELISA at Day 21 (after a booster vaccine dose) compared to pre-vaccine values. Secondary Objectives To evaluate the relationship between baseline vitamin levels and pneumococcal or hepatitis A vaccine antibody responses (based on in commercial ELISAs) at Days 0 and 21. To evaluate the influence of vitamin A supplementation on hepatitis vaccine immunogenicity based on changes in antibody scores in a commercial ELISA at Day 21 compared to pre-vaccine values. To evaluate relationships between total serum antibodies (based on individual IgM, IgG1, IgG2, IgG3, IgG4, and IgA scores in a Luminex assay) at Day 0 and changes between Days 0 and 21 with baseline (Day 0) vitamin levels in young children, and with vitamin A supplementation.

Detailed Description
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Children between the ages of 1 and 4 years old (inclusive) will be enrolled. All will receive PCV and hepatitis A vaccination. Those randomized to the treatment arm will receive 10,000 IU orally at the time of vaccination, while those randomized to the control arm will only receive vaccines. Vitamin levels and antibody responses towards the vaccines will be measured at screening, Day 0 (vaccination day) and Day +21. Children will be randomized using a stratified permuted block method.

Official Title
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A Randomized Controlled Trial of Antibody Responses by Vitamin Supplementation at the Time of Pneumococcus Vaccination in Children

Conditions
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Healthy Participants

Intervention / Treatment
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* Biological: Vitamin A supplementation
* Biological: No vitamin A supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 1 and 4 years old (inclusive) at the time of enrollment Fully weaned from breast-feeding or formula-feeding for at least 4 weeks prior to vaccination date (Day 0). Received at least 2 doses of Prevnar-13 vaccination Parent or legal guardian willing and able to provide informed consent. Exclusion Criteria: Current use of investigational or immunosuppressive drugs (e.g., steroids) at the time of enrollment Parent/guardian planning to continue (or initiate) the administration of daily vitamin A, vitamin D, or multivitamin to the child during the study period. Evidence of developmental delay or evolving neurological disorders at screening. Current use of antibiotics or antivirals at enrollment. Currently receiving cancer related treatment. History of heart, kidney, or chronic respiratory condition (e.g., asthma) conditions. History of diabetes. Acute febrile illness [e.g., >100.0F (37.8oC) oral] illness within 3 days prior to enrollment. Received a previous PCV13 vaccine within 2 months of the enrollment date (Day 0). Received hepatitis A vaccine previously. Ever had a life-threatening allergic reaction to a dose of PCV13 vaccine, to an earlier pneumococcal vaccine called PCV7, or to any vaccine containing diptheria toxoid (for example, DTaP).

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>PCV (Prevnar-13 Vaccine) and the hepatitis A vaccine (Havrix Vaccine) plus a liquid oral vitamin A supplementation | Biological: Vitamin A supplementation<br>* liquid oral vitamin A supplementation<br>|
| Experimental: Control group<br>PCV (Prevnar-13 Vaccine) and the hepatitis A vaccine (Havrix Vaccine) only, 'No vitamin A supplementation' | Biological: No vitamin A supplementation<br>* No vitamin A supplementation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate in two arms | The seroconversion rate, defined as the proportion of 4X increases or conversion from undetectable to detectable response in vaccine-specific antibody after vaccinations (Day 21) versus the baseline (Day 0) antibody level in intervention and control groups will be estimated and 95% confidence interval will be described for both groups. The 95% confidence interval will serve as a measure of precision of the seroconversion rate estimate. Chi-square test will be performed to make the comparison between two arms. | Measured at Day 21 | 
| Sera titer ratio | Titer ratios will be summarized with descriptive statistics. Two-sample tests (t-test or Wilcoxon rank-sum test) will be applied whenever appropriate | Measured at Day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spearman's correlation coefficient of vaccine antibody responses at days 0 with baseline vitamin levels for each arm. | Spearman's correlation coefficient. | Measured at Day 21 | 
| Spearman's correlation coefficient of vaccine antibody responses at days 21 with baseline vitamin levels for each arm. | Spearman's correlation coefficient. | Measured at Day 21 | 
| Proportion of subjects showing 4X increases or conversion from undetectable to detectable response in B cell responses after vaccinations for both groups, and by VA/VD stratum. | The proportion difference with 95% confidence interval will be reported via Chi-square test or Fisher's test. | Measured at Day 21 | 
| Correlation of immunoglobulin M (IgM) antibody (measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 1 (IgG1) antibody (measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 2 (IgG2) antibody (measured by Luminex assay | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 3 (IgG3) antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 4 (IgG4)antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin A (IgA) antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient | Measured at Day 21 | 
| Correlation of immunoglobulin M (IgM) antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 2 (IgG2) antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 3 (IgG3) antibody (measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin G subclass 4 (IgG4) antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 
| Correlation of immunoglobulin A (IgA) antibody(measured by Luminex assay) | Correlation will be expressed as Spearman's correlation coefficient. | Measured at Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Vitamin Supplements, PCV13, Hepatitis A vaccine