Clinical trial NCT03859687: Trial of Antibody Responses by Vitamin Supplementation
Official title: A Randomized Controlled Trial of Antibody Responses by Vitamin Supplementation at the Time of Pneumococcus Vaccination in Children
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Children
Vitamin Supplements
PCV13
Hepatitis A vaccine
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: The Gerber Foundation
First posted: 2019-03-01
Enrollment: 22
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Seroconversion rate in two arms
timeFrame: Measured at Day 21
measure: Sera titer ratio
timeFrame: Measured at Day 21
Secondary outcomes:
measure: Spearman's correlation coefficient of vaccine antibody responses at days 0 with baseline vitamin levels for each arm.
timeFrame: Measured at Day 21
measure: Spearman's correlation coefficient of vaccine antibody responses at days 21 with baseline vitamin levels for each arm.
timeFrame: Measured at Day 21
measure: 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.
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin M (IgM) antibody (measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 1 (IgG1) antibody (measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 2 (IgG2) antibody (measured by Luminex assay
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 3 (IgG3) antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 4 (IgG4)antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin A (IgA) antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin M (IgM) antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 2 (IgG2) antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 3 (IgG3) antibody (measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin G subclass 4 (IgG4) antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
measure: Correlation of immunoglobulin A (IgA) antibody(measured by Luminex assay)
timeFrame: Measured at Day 21
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Nehali Patel, MD
role: PRINCIPAL_INVESTIGATOR
References: