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

Not Applicable

Completed

• Conditions: Tuberculosis
• Interventions: Dietary Supplement: Vitamin D3 (cholecalciferol)

• Registration Number: NCT01288950
• Lead Sponsor: University of California, San Diego

Brief Summary

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.

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 Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-01
• Study First Submitted QC: 2011-02-02
• Study First Posted: 2011-02-03
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-20
• Last Update Posted: 2012-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin D3	Vitamin D3 (cholecalciferol)	-

Primary Outcome Measures

Name	Time	Method
Bacille-Calmette-Guerin (BCG) vaccine efficacy	1 year

Secondary Outcome Measures

Name	Time	Method
Bacille-Calmette-Guerin (BCG) vaccine efficacy	1 year	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.
Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels	2 months	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.

Trial Locations

Locations (1)

Tijuana General Hospital; 🇲🇽 Tijuana, Baja California, Mexico