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

University of California San Diego

Status: Completed

Conditions: Tuberculosis

Treatments: Dietary Supplement: Vitamin D3 (cholecalciferol)

Study type: Interventional

Funder types: Other

Identifiers

NCT01288950

NR-0138

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: Under 3 days old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

49 participants in 2 patient groups

Vitamin D3

Experimental group

Treatment:

Dietary Supplement: Vitamin D3 (cholecalciferol)

Placebo

No Intervention group