Vitamin D Supplementation Enhances Immune Response to Bacille-Calmette-Guerin (BCG) Vaccination in Infants (BCG-25-D)

Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants

The purpose of this study is to determine whether a single oral dose of vitamin D given to infants prior to Bacille-Calmette-Guerin (BCG) vaccination will enhance the immune response to BCG vaccination.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Dietary supplement: Vitamin D3 (cholecalciferol)

Detailed Description

In 2000, there were an estimated 884,000 cases of tuberculosis (TB) in children with many developing severe, disseminated disease. Widespread immunization with Bacille-Calmette-Guerin (BCG) vaccine has not been effective in preventing primary TB infection or in halting the progression from latent to active disease. Poor vaccine efficacy has prompted investigators to develop novel TB vaccines and to experiment with enhancing the immune response to the current BCG vaccine.

Increasing data indicate that children with low vitamin D levels and specific genetic variants that lower functional levels of vitamin D are at increased risk for severe tuberculosis. Elegant studies investigating Mycobacterium tuberculosis (Mtb) infection have shown that mycobacteria are able to reside in endosomes within macrophages by preventing endosome-lysosome fusion; a critical step in autophagy, a cellular process used to recycle cytoplasmic organelles and proteins, and to degrade microbial organisms including Mtb. In-vitro studies have shown that vitamin D increases autophagy and triggers the production of antimicrobial peptides including cathelicidin. This leads to increased intracellular killing of Mtb and increased Mtb antigen presentation to the immune system. Anti-tuberculous vaccines that over-express Mtb antigens generate a stronger immune response than wild type BCG vaccine.

The investigators hypothesis is that a single oral dose of vitamin D3 (cholecalciferol) given to infants prior to BCG administration will enhance the immune response to vaccination through improved MHC class I and class II presentation of the vaccine.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Baja California
    • Tijuana, Baja California, Mexico
      • Tijuana General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy mothers > 18 years of age
• Term, healthy infants eligible to receive the Bacille-Calmette- Guerin (BCG) vaccine

Exclusion Criteria:

• Recent maternal history of tuberculosis (within 1 year) or active tuberculosis
• Known maternal human immuno-deficiency virus (HIV) infection
• Maternal fever or chorio-amnionitis
• Maternal use of vitamin D, steroids or immuno-regulatory medications
• Household member with active tuberculosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Placebo
Experimental: Vitamin D3	Dietary supplement: Vitamin D3 (cholecalciferol); A single oral dose of 50,000 IU of vitamin D3 (cholecalciferol) will be given prior to Bacille-Calmette-Guerin (BCG) vaccination; Other Names: Carlson Ddrops liquid vitamin D3 2,000 IU per drop

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacille-Calmette-Guerin (BCG) vaccine efficacy	BCG vaccine efficacy will be assessed by measuring the host immune response against BCG at 2 months, 6 months and one year after BCG immunization. A whole blood assay will be used to measure multiple cytokines and mycobacterial growth suppression.	2 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy		6 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy		1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels	Serum 25 hydroxy (OH) vitamin D levels will be measured prior to vitamin D supplementation and at 2 months, 6 months and one year after BCG immunization. The investigators will also determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect baseline vitamin D levels and alter the response to vitamin D supplementation.	2 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy	The investigators will determine whether specific host genetic variants including the Fok-I(rs2228570T/C), Bsm-I(rs1544410A/G), GC(rs2282679A/C), DHCR7(rs12785878G/T) and CYP2R1 (rs10741657A/G) polymorphisms affect the response to BCG vaccine in infants receiving either vitamin D or placebo.	1 year

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Thrasher Research Fund
• Investigators: Study Chair: Stephen Spector, MD, University of California, San Diego; Principal Investigator: Amaran Moodley, M.D, University of California, San Diego

Publications and helpful links

General Publications

• Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: February 1, 2011
• First Submitted That Met QC Criteria: February 2, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Estimate): August 22, 2012
• Last Update Submitted That Met QC Criteria: August 20, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Vitamin D; BCG vaccine; Tuberculosis; Cholecalciferol
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: NR-0138