Clinical trial NCT01288950: Vitamin D Supplementation Enhances Immune Response to Bacille-Calmette-Guerin (BCG) Vaccination in Infants
Official title: Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
Keywords: BCG vaccine
Vitamin D
Cholecalciferol
Tuberculosis
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2011-02-03
Enrollment: 49
Sex: ALL
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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 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

Primary outcomes:
measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy
timeFrame: 2 months
measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy
timeFrame: 6 months
measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy
timeFrame: 1 year
Secondary outcomes:
measure: Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels
timeFrame: 2 months
measure: Bacille-Calmette-Guerin (BCG) vaccine efficacy
timeFrame: 1 year
Other outcomes:
Locations:
city: Tijuana
country: Mexico
facility: Tijuana General Hospital
state: Baja California
Study officials:
affiliation: University of California, San Diego
name: Stephen Spector, MD
role: STUDY_CHAIR
affiliation: University of California, San Diego
name: Amaran Moodley, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huey SL, Acharya N, Silver A, Sheni R, Yu EA, Pena-Rosas JP, Mehta S. Effects of oral vitamin D supplementation on linear growth and other health outcomes among children under five years of age. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD012875. doi: 10.1002/14651858.CD012875.pub2.