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

Sponsor

University of California, San Diego (Other)

Overall Status

Completed

CT.gov ID

NCT01288950

Collaborator

Thrasher Research Fund (Other)

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Dietary Supplement: Vitamin D3 (cholecalciferol)	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants

Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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
No Intervention: Placebo

Arm

Intervention/Treatment

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

No Intervention: Placebo

Outcome Measures

Primary Outcome Measures

Bacille-Calmette-Guerin (BCG) vaccine efficacy [2 months]
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.
Bacille-Calmette-Guerin (BCG) vaccine efficacy [6 months]
Bacille-Calmette-Guerin (BCG) vaccine efficacy [1 year]

Secondary Outcome Measures

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.
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.