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

This study has been completed.
Sponsor:
Collaborator:
Thrasher Research Fund
Information provided by (Responsible Party):
Amaran Moodley, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01288950
First received: February 1, 2011
Last updated: August 20, 2012
Last verified: August 2012

February 1, 2011
August 20, 2012
February 2011
July 2012   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01288950 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Vitamin D Supplementation Enhances Immune Response to Bacille-Calmette-Guerin (BCG) Vaccination in Infants
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Tuberculosis
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
  • Experimental: Vitamin D3
    Intervention: Dietary Supplement: Vitamin D3 (cholecalciferol)
  • No Intervention: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
49
July 2012
July 2012   (final data collection date for primary outcome measure)

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
Both
up to 3 Days
Yes
Contact information is only displayed when the study is recruiting subjects
Mexico
 
NCT01288950
NR-0138
No
Amaran Moodley, University of California, San Diego
University of California, San Diego
Thrasher Research Fund
Study Chair: Stephen Spector, MD University of California, San Diego
Principal Investigator: Amaran Moodley, M.D University of California, San Diego
University of California, San Diego
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP