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

Tuberculosis Clinical Trial

— BCG-25-D  

Official title:

Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01288950
• Other study ID #: NR-0138
• Status: Completed
• Phase: N/A
• First received: February 1, 2011
• Last updated: August 20, 2012
• Start date: February 2011
• Est. completion date: July 2012

Study information

• Verified date: August 2012
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 3 Days

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Tuberculosis

Intervention

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

Locations

Country	Name	City	State
Mexico	Tijuana General Hospital	Tijuana	Baja California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Diego	Thrasher Research Fund

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Bacille-Calmette-Guerin (BCG) vaccine efficacy		6 months	No
Primary	Bacille-Calmette-Guerin (BCG) vaccine efficacy		1 year	No
Secondary	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	No
Secondary	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	No