TuberculosisBCG-25-DNCT01288950
Vitamin D Supplementation Enhances Immune Response to Bacille-Calmette-Guerin (BCG) Vaccination in Infants
A study testing Vitamin D3 (cholecalciferol) in people with Tuberculosis, run by University of California, San Diego at 1 site in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 3 daysHealthy volunteers can take part
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Vitamin D3 (cholecalciferol)
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteMexico
- Study dates
- Feb 2011to Jul 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 3 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy mothers > 18 years of age
- Term, healthy infants eligible to receive the Bacille-Calmette- Guerin (BCG) vaccine
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Tuberculosis
- Being tested
- Vitamin D3 (cholecalciferol)
- Keywords
- BCG vaccine, Vitamin D, Cholecalciferol, Tuberculosis
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3 (cholecalciferol)Dietary supplement
Also called Carlson Ddrops liquid vitamin D3 2,000 IU per drop
A single oral dose of 50,000 IU of vitamin D3 (cholecalciferol) will be given prior to Bacille-Calmette-Guerin (BCG) vaccination
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D3 | Experimental | Not described Receives: Dietary Supplement: Vitamin D3 (cholecalciferol) |
| Placebo | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bacille-Calmette-Guerin (BCG) vaccine efficacy
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.
Measured: 2 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy
Measured: 6 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy
Measured: 1 year
Secondary outcomes (2)
Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels
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.
Measured: 2 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Principal investigator, Amaran Moodley, University of California, San Diego
- Investigators
- Stephen Spector, MD, Study chair, University of California, San DiegoAmaran Moodley, M.D, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01288950
- Sponsor's protocol ID
- NR-0138
- Acronym
- BCG-25-D
- Status last verified
- Aug 2012
- First submitted
- 1 Feb 2011
- Last updated
- 22 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 33305842
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Supplementation Enhances Immune Response to BCG Vaccination in Infants
- ClinicalTrials.gov ID
- NCT01288950
- Acronym / sponsor ID
- BCG-25-D / NR-0138
- Conditions
- Tuberculosis
- Keywords
- BCG vaccine, Vitamin D, Cholecalciferol, Tuberculosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- Feb 2011
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 3 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D3 | Experimental | Dietary Supplement: Vitamin D3 (cholecalciferol) |
| Placebo | No intervention | – |
Who may qualify
- Ages
- Up to 3 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Healthy mothers > 18 years of age
- Term, healthy infants eligible to receive the Bacille-Calmette- Guerin (BCG) vaccine
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3 (cholecalciferol)Also: Carlson Ddrops liquid vitamin D3 2,000 IU per dropA single oral dose of 50,000 IU of vitamin D3 (cholecalciferol) will be given prior to Bacille-Calmette-Guerin (BCG) vaccination | Dietary supplement | Vitamin D3 |
Primary outcome
Bacille-Calmette-Guerin (BCG) vaccine efficacy
Time frame: 2 months
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
Bacille-Calmette-Guerin (BCG) vaccine efficacy
Time frame: 1 year
2 secondary outcomes
Effect of a single dose of 50,000 IU vitamin D3 on serum vitamin D levels
Time frame: 2 months
Bacille-Calmette-Guerin (BCG) vaccine efficacy
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2012.
- Derived from this study: PubMed 33305842Huey 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Spector, MD study chair
University of California, San Diego
Amaran Moodley, M.D principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin D3 (cholecalciferol) in people with Tuberculosis, run by University of California, San Diego at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bacille-Calmette-Guerin (BCG) vaccine efficacy (time frame: 2 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01288950, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2012.