Vitamin D Supplementation Enhances Immune Response to Bacille-Calmette-Guerin (BCG) Vaccination in Infants (BCG-25-D)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants|
- Bacille-Calmette-Guerin (BCG) vaccine efficacy [ Time Frame: 2 months ] [ Designated as safety issue: No ]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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Bacille-Calmette-Guerin (BCG) vaccine efficacy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels [ Time Frame: 2 months ] [ Designated as safety issue: No ]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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
|Study Start Date:||February 2011|
|Study Completion Date:||July 2012|
|Primary Completion Date:||July 2012 (Final data collection date for primary outcome measure)|
|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 Name: Carlson Ddrops liquid vitamin D3 2,000 IU per drop
|No Intervention: Placebo|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01288950
|Tijuana General Hospital|
|Tijuana, Baja California, Mexico|
|Study Chair:||Stephen Spector, MD||University of California, San Diego|
|Principal Investigator:||Amaran Moodley, M.D||University of California, San Diego|