Trial of Antibody Responses by Vitamin Supplementation

• ClinicalTrials.gov Identifier: NCT03859687
• Recruitment Status: Active, not recruiting
• First Posted: March 1, 2019
• Last Update Posted: March 2, 2021
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: The Gerber Foundation
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Tracking Information

• First Submitted Date: February 22, 2019
• First Posted Date: March 1, 2019
• Last Update Posted Date: March 2, 2021
• Actual Study Start Date: August 19, 2019
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2019)

• Seroconversion rate in two arms [ Time Frame: Measured at Day 21 ]
  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.
• Sera titer ratio [ Time Frame: Measured at Day 21 ]
  Titer ratios will be summarized with descriptive statistics. Two-sample tests (t-test or Wilcoxon rank-sum test) will be applied whenever appropriate

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 4, 2019)

• Spearman's correlation coefficient of vaccine antibody responses at days 0 with baseline vitamin levels for each arm. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of vaccine antibody responses at days 21 with baseline vitamin levels for each arm. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• 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. [ Time Frame: Measured at Day 21 ]
  The proportion difference with 95% confidence interval will be reported via Chi-square test or Fisher's test.
• Correlation of immunoglobulin M (IgM) antibody (measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 1 (IgG1) antibody (measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 2 (IgG2) antibody (measured by Luminex assay [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 3 (IgG3) antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 4 (IgG4)antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin A (IgA) antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient
• Correlation of immunoglobulin M (IgM) antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 2 (IgG2) antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 3 (IgG3) antibody (measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin G subclass 4 (IgG4) antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.
• Correlation of immunoglobulin A (IgA) antibody(measured by Luminex assay) [ Time Frame: Measured at Day 21 ]
  Correlation will be expressed as Spearman's correlation coefficient.

Original Secondary Outcome Measures (submitted: February 27, 2019)

• Spearman's correlation coefficient of vaccine antibody responses at days 0 with baseline vitamin levels for each arm. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of vaccine antibody responses at days 21 with baseline vitamin levels for each arm. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• 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. [ Time Frame: Measured at Day 21 ]
  The proportion difference with 95% confidence interval will be reported via Chi-square test or Fisher's test.
• Spearman's correlation coefficient of IgM score (Luminex assay) at day 0 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG1 score (Luminex assay) at day 0 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG2 score (Luminex assay) at day 0 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG3 score (Luminex assay) at day 0 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG4 score (Luminex assay) at day 0 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgA score (Luminex assay) at day 0 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgM score (Luminex assay) at day 21 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG1 score (Luminex assay) at day 21 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG2 score (Luminex assay) at day 21 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG3 score (Luminex assay) at day 21 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgG4 score (Luminex assay) at day 21 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.
• Spearman's correlation coefficient of IgA score (Luminex assay) at day 21 with baseline vitamin levels overall, by treatment groups, and stratified by baseline vitamin levels. [ Time Frame: Measured at Day 21 ]
  Spearman's correlation coefficient.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Healthy Participants

Intervention

• Biological: Vitamin A supplementation
  liquid oral vitamin A supplementation
• Biological: No vitamin A supplementation
  No vitamin A supplementation

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: February 27, 2019): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 12, 2024
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 4 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03859687
• Other Study ID Numbers: PCVIT
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: St. Jude Children's Research Hospital
• Study Sponsor: St. Jude Children's Research Hospital
• Collaborators: The Gerber Foundation

Investigators

• Principal Investigator: Nehali Patel, MD; St. Jude Children's Research Hospital

• PRS Account: St. Jude Children's Research Hospital
• Verification Date: March 2021