Trial of Antibody Responses by Vitamin Supplementation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Biological: Vitamin A supplementation; Biological: No 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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Nehali Patel, MD; Phone Number: 1-866-278-5833; Email: referralinfo@stjude.org

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • St. Jude Children's Research Hospital
      • Contact: Nehali Patel, MD; Phone Number: 866-278-5833; Email: referralinfo@stjude.org
      • Principal Investigator: Nehali Patel, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 4 years (Child)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: The Gerber Foundation
• Investigators: Principal Investigator: Nehali Patel, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 12, 2026

Study Registration Dates

• First Submitted: February 22, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Children; PCV13; Hepatitis A vaccine; Vitamin Supplements
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Antioxidants; Anticarcinogenic Agents; Vitamins; Vitamin A; Retinol palmitate
• Other Study ID Numbers: PCVIT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes