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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
History of Changes
  Purpose

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 Intervention
Tuberculosis
 Dietary Supplement: Vitamin D3 (cholecalciferol)

Study Type: Interventional
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Enrollment: 49
Study Start Date: February 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   up to 3 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01288950

Locations
Mexico
Tijuana General Hospital
Tijuana, Baja California, Mexico
Sponsors and Collaborators
University of California, San Diego
Thrasher Research Fund
Investigators
Study Chair: Stephen Spector, MD University of California, San Diego
Principal Investigator: Amaran Moodley, M.D University of California, San Diego
  More Information

No publications provided

Responsible Party: Amaran Moodley, Research Fellow, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01288950     History of Changes
Other Study ID Numbers: NR-0138
Study First Received: February 1, 2011
Last Updated: August 20, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
BCG vaccine
Vitamin D
Cholecalciferol
Tuberculosis

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Cholecalciferol
Vitamin D
 Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on May 22, 2013