SepsisPhase 2/3NCT02085590
Effects of BCG on Immune Response
A Phase 2/3 study testing BCG vaccine and Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenously in people with Sepsis, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In the present study, we want to investigate whether BCG-vaccination enhances the innate immune response in humans in vivo during (single) human endotoxemia. In a future experiment we will investigate whether BCG-vaccination can reverse the tolerant state observed upon a second LPS administration. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Sepsis
- What is being tested?
- BCG vaccine and Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenously
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2014to Nov 2014
- Phase
- Phase 2/3
- 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 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent
- Age ≥18 and ≤35 yrs
- Male
- Healthy
Who cannot join
- Use of any medication
- History of BCG-vaccination
- Vaccination other than BCG, within 3 months prior to study or within study period
- Tuberculin skin test (Mantoux) in last year
- Smoking
- Previous spontaneous vagal collapse
Show all 20Show fewer
- History of atrial or ventricular arrhythmia
- (Family) history of myocardial infarction or stroke under the age of 65 years
- Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block
- Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
- Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
- Renal impairment (defined as plasma creatinin >120 μmol/l)
- Liver enzyme abnormalities or positive hepatitis serology
- Medical history of any disease associated with immune deficiency
- CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxin administration
- Participation in a drug trial or donation of blood 3 months prior to the LPS challenge
- Previous participation in a LPS trial
- Use of recreational drugs within 21 days prior to experiment day
- Recent hospital admission or surgery with general anaesthesia (<3 months)
- Disagreement of participant with informing general practitioner of participation in this study
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Medical Centre, Intensive Care
Nijmegen, 6525 GA
About this study
Official title: The Effects of BCG-vaccination on the Innate Immune Response in Healthy Volunteers. Pilot Proof-of-principle Studie
In the present study, we want to investigate whether BCG-vaccination enhances the innate immune response in humans in vivo during (single) human endotoxemia.
In a future experiment we will investigate whether BCG-vaccination can reverse the tolerant state observed upon a second LPS administration.
Our goal is to ultimately translate our results into clinic applications to reverse for example sepsis-induced immunoparalysis.
Read the detailed description
Sepsis is a major medical challenge associated with a high mortality rate. Release of pro-inflammatory mediators can result in hemodynamic instability, coagulation abnormalities and end-organ dysfunction. Previous strategies have aimed to treat sepsis by inhibition of pro-inflammatory mediators, however, most of these approaches have failed. This might be due to the fact that the majority of septic patients do not succumb to the initial pro-inflammatory "hit", but die at a later time-point in a pronounced immunosuppressive state. This so-called 'immunoparalysis', which renders patients extremely vulnerable to secondary infections, results from the triggering of counter-regulatory anti-inflammatory pathways along with the pro-inflammatory response, already starting in the beginning of sepsis. Immunoparalysis is increasingly being recognized as the overriding immune dysfunction during sepsis. As a consequence, reconstitution of immunocompetence is now emerging as a new and promising therapeutic target to improve outcome in sepsis patients.
Bacille Calmette-Guérin (BCG) is one of the most commonly administered vaccines worldwide. In addition to protection against tuberculosis, evidence suggests that BCG immunization has a number of additional beneficial non-specific immunological effects, hereby protecting against infections with pathogens other than tuberculosis. The underlying immunologic mechanisms are not fully elucidated. Recently it was demonstrated that monocytes can be functionally reprogrammed to an enhanced and lasting phenotype after vaccination with BCG. Production of pro-inflammatory cytokines by monocytes isolated from volunteers after BCG vaccination, was found to be enhanced upon ex vivo stimulation with non-related pathogens, even months after BCG vaccination. The observed effects are proposed to be due to modulation of the innate immune system in a process called 'trained immunity'. Upon stimulation with a pathogen, the innate immune system becomes primed and is able to react faster and more efficient to a secondary (and non-related) stimulus, even months later. Monocyte "training" was shown to rely on epigenetic reprogramming, namely increased methylation of histone 3 at lysine 4 (H3K4me3) at the level of cytokine and TLR4 gene promoter regions.
Considering these potentiating effects of BCG on innate host defense, it could be a viable treatment option for sepsis-induced immunoparalysis. However, the effects of BCG vaccination on the innate immune response in humans have hitherto only been shown ex vivo. It has yet to be established whether these findings can be extrapolated to the human in vivo situation, because previous data from our group indicates that ex vivo measurements do not accurately reflect the in vivo situation. The human endotoxemia model, in which healthy volunteers receive lipopolysaccharide (LPS) derived from Escherichia coli, is widely used to study the effects of systemic inflammation in humans in vivo and is considered a safe and highly reproducible method to investigate the innate immune response. Furthermore, LPS administration results in a hyporesponsive state towards a second LPS administration called "endotoxin tolerance", which resembles sepsis-induced immunoparalysis, and can thus be used as a model to investigate therapeutic interventions to reverse this condition.
The intended target group for this novel therapy, sepsis patients, are immunocompromised. Therefore, use of a live attenuated vaccine such as BCG could present a risk of disseminated mycobacterial infection. Therefore, we will use γ-irradiated (inactivated) BCG vaccine in this study. Recent, yet unpublished results of the group of Prof. Netea have shown that the effects of γ-irradiated BCG on monocyte training are comparable to those of the live vaccine. Furthermore, a study by the group of Prof. Netea (CMO 2013/319) with this type and dose of γ-irradiated BCG in healthy volunteers to study ex vivo responses has been previously approved by the ethics committee.
Study design:
A randomized double-blind placebo-controlled pilot study in healthy human volunteers during experimental endotoxemia.
In this pilot study, we will enrol 20 subjects. On day 1, 10 subjects will receive γ-irradiated BCG-vaccination and 10 subjects will receive placebo. On day 6, all subjects will undergo experimental endotoxemia.
- Conditions
- Sepsis
- Being tested
- BCG vaccine, Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenously
- Keywords
- BCG vaccine, Sepsis, Immunity
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccineBiological
Also called BCG vaccine SSI, Bacille Calmette-Guérin, RVG 17661
Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenouslyBiological
Also called Lipopolysaccharide, LPS, Endotoxin derived from E. Coli
| Study group | Role | What they receive |
|---|---|---|
| BCG vaccine | Active comparator | BCG vaccine SSI, 0.75mg/ml, injection 0.1 cc intradermal Receives: Biological: BCG vaccine; Biological: Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenously |
| NaCl 0.9% | Placebo comparator | injection 0.1 cc intradermal Receives: Biological: Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenously |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the effects of γ-irradiated BCG-vaccination on the in vivo innate immune responses induced by human endotoxemia.
This will be determined by measuring plasma levels of various pro- and anti-inflammatory cytokines and assessing the difference in the Lipopolysacharide (LPS)-induced cytokine response between γ-irradiated BCG-vaccinated subjects and placebo-treated control subjects.
Measured: Several time points within 1 month after vaccination
Secondary outcomes (5)
To determine the effects of γ-irradiated BCG-vaccination on ex vivo responsiveness of leukocytes to various inflammatory stimuli.
Measured: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on the phenotype of circulating monocytes
e.g. expression pattern of cell-surface receptors by use of flow cytometry
Measured: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on inflammatory transcriptional pathways (by use of qPCR/microarrays)
Measured: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on epigenetic changes, including H3K4 trimethylation, in circulating immune cells.
Measured: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on LPS-induced clinical symptoms (illness score) and hemodynamic/temperature changes.
Measured: Several time points within an 8 hour period following LPS-exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionOct 2014
- Study completionNov 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthijs Kox, Radboud University Medical Center
- Investigators
- Peter Pickkers, Prof., Study director, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02085590
- Sponsor's protocol ID
- BCG-LPS
- Status last verified
- May 2015
- First submitted
- 11 Mar 2014
- Last updated
- 13 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
PubMed 11445675Leentjens J, Kox M, van der Hoeven JG, Netea MG, Pickkers P. Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? Am J Respir Crit Care Med. 2013 Jun 15;187(12):1287-93. doi: 10.1164/rccm.201301-0036CP.
PubMed 23590272Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17537-42. doi: 10.1073/pnas.1202870109. Epub 2012 Sep 17.
PubMed 22988082Kleinnijenhuis J, Quintin J, Preijers F, Benn CS, Joosten LA, Jacobs C, van Loenhout J, Xavier RJ, Aaby P, van der Meer JW, van Crevel R, Netea MG. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun. 2014;6(2):152-8. doi: 10.1159/000355628. Epub 2013 Oct 30.
PubMed 24192057Hamers LA, Kox M, Arts RJ, Blok B, Leentjens J, Netea MG, Pickkers P. Gamma-irradiated bacille Calmette-Guerin vaccination does not modulate the innate immune response during experimental human endotoxemia in adult males. J Immunol Res. 2015;2015:261864. doi: 10.1155/2015/261864. Epub 2015 Mar 26.
PubMed 25883989
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of BCG-vaccination on the Innate Immune Response in Healthy Volunteers. Pilot Proof-of-principle Studie
- ClinicalTrials.gov ID
- NCT02085590
- Acronym / sponsor ID
- BCG-LPS
- Conditions
- Sepsis
- Keywords
- BCG vaccine, Sepsis, Immunity
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 13 Mar 2014 (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.
In the present study, we want to investigate whether BCG-vaccination enhances the innate immune response in humans in vivo during (single) human endotoxemia.
In a future experiment we will investigate whether BCG-vaccination can reverse the tolerant state observed upon a second LPS administration.
Our goal is to ultimately translate our results into clinic applications to reverse for example sepsis-induced immunoparalysis.
Detailed description
Sepsis is a major medical challenge associated with a high mortality rate. Release of pro-inflammatory mediators can result in hemodynamic instability, coagulation abnormalities and end-organ dysfunction. Previous strategies have aimed to treat sepsis by inhibition of pro-inflammatory mediators, however, most of these approaches have failed. This might be due to the fact that the majority of septic patients do not succumb to the initial pro-inflammatory "hit", but die at a later time-point in a pronounced immunosuppressive state. This so-called 'immunoparalysis', which renders patients extremely vulnerable to secondary infections, results from the triggering of counter-regulatory anti-inflammatory pathways along with the pro-inflammatory response, already starting in the beginning of sepsis. Immunoparalysis is increasingly being recognized as the overriding immune dysfunction during sepsis. As a consequence, reconstitution of immunocompetence is now emerging as a new and promising therapeutic target to improve outcome in sepsis patients.
Bacille Calmette-Guérin (BCG) is one of the most commonly administered vaccines worldwide. In addition to protection against tuberculosis, evidence suggests that BCG immunization has a number of additional beneficial non-specific immunological effects, hereby protecting against infections with pathogens other than tuberculosis. The underlying immunologic mechanisms are not fully elucidated. Recently it was demonstrated that monocytes can be functionally reprogrammed to an enhanced and lasting phenotype after vaccination with BCG. Production of pro-inflammatory cytokines by monocytes isolated from volunteers after BCG vaccination, was found to be enhanced upon ex vivo stimulation with non-related pathogens, even months after BCG vaccination. The observed effects are proposed to be due to modulation of the innate immune system in a process called 'trained immunity'. Upon stimulation with a pathogen, the innate immune system becomes primed and is able to react faster and more efficient to a secondary (and non-related) stimulus, even months later. Monocyte "training" was shown to rely on epigenetic reprogramming, namely increased methylation of histone 3 at lysine 4 (H3K4me3) at the level of cytokine and TLR4 gene promoter regions.
Considering these potentiating effects of BCG on innate host defense, it could be a viable treatment option for sepsis-induced immunoparalysis. However, the effects of BCG vaccination on the innate immune response in humans have hitherto only been shown ex vivo. It has yet to be established whether these findings can be extrapolated to the human in vivo situation, because previous data from our group indicates that ex vivo measurements do not accurately reflect the in vivo situation. The human endotoxemia model, in which healthy volunteers receive lipopolysaccharide (LPS) derived from Escherichia coli, is widely used to study the effects of systemic inflammation in humans in vivo and is considered a safe and highly reproducible method to investigate the innate immune response. Furthermore, LPS administration results in a hyporesponsive state towards a second LPS administration called "endotoxin tolerance", which resembles sepsis-induced immunoparalysis, and can thus be used as a model to investigate therapeutic interventions to reverse this condition.
The intended target group for this novel therapy, sepsis patients, are immunocompromised. Therefore, use of a live attenuated vaccine such as BCG could present a risk of disseminated mycobacterial infection. Therefore, we will use γ-irradiated (inactivated) BCG vaccine in this study. Recent, yet unpublished results of the group of Prof. Netea have shown that the effects of γ-irradiated BCG on monocyte training are comparable to those of the live vaccine. Furthermore, a study by the group of Prof. Netea (CMO 2013/319) with this type and dose of γ-irradiated BCG in healthy volunteers to study ex vivo responses has been previously approved by the ethics committee.
Study design:
A randomized double-blind placebo-controlled pilot study in healthy human volunteers during experimental endotoxemia.
In this pilot study, we will enrol 20 subjects. On day 1, 10 subjects will receive γ-irradiated BCG-vaccination and 10 subjects will receive placebo. On day 6, all subjects will undergo experimental endotoxemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BCG vaccine | Active comparator | Biological: BCG vaccine, Biological: Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenouslyBCG vaccine SSI, 0.75mg/ml, injection 0.1 cc intradermal |
| NaCl 0.9% | Placebo comparator | Biological: Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenouslyinjection 0.1 cc intradermal |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Written informed consent
- Age ≥18 and ≤35 yrs
- Male
- Healthy
Key exclusion criteria (20 listed)
- Use of any medication
- History of BCG-vaccination
- Vaccination other than BCG, within 3 months prior to study or within study period
- Tuberculin skin test (Mantoux) in last year
- Smoking
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 |
|---|---|---|
| BCG vaccineAlso: BCG vaccine SSI, Bacille Calmette-Guérin, RVG 17661 | Biological | BCG vaccine |
| Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenouslyAlso: Lipopolysaccharide, LPS, Endotoxin derived from E. Coli | Biological | BCG vaccine, NaCl 0.9% |
Primary outcome
To determine the effects of γ-irradiated BCG-vaccination on the in vivo innate immune responses induced by human endotoxemia.
Time frame: Several time points within 1 month after vaccination
This will be determined by measuring plasma levels of various pro- and anti-inflammatory cytokines and assessing the difference in the Lipopolysacharide (LPS)-induced cytokine response between γ-irradiated BCG-vaccinated subjects and placebo-treated control subjects.
5 secondary outcomes
To determine the effects of γ-irradiated BCG-vaccination on ex vivo responsiveness of leukocytes to various inflammatory stimuli.
Time frame: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on the phenotype of circulating monocytes
Time frame: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on inflammatory transcriptional pathways (by use of qPCR/microarrays)
Time frame: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on epigenetic changes, including H3K4 trimethylation, in circulating immune cells.
Time frame: Several time points within 1 month after vaccination
To determine the effects of γ-irradiated BCG-vaccination on LPS-induced clinical symptoms (illness score) and hemodynamic/temperature changes.
Time frame: Several time points within an 8 hour period following LPS-exposure
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 13 May 2015.
- Background: PubMed 11445675Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001 Jul;29(7):1303-10. doi: 10.1097/00003246-200107000-00002.
- Background: PubMed 23590272Leentjens J, Kox M, van der Hoeven JG, Netea MG, Pickkers P. Immunotherapy for the adjunctive treatment of sepsis: from immunosuppression to immunostimulation. Time for a paradigm change? Am J Respir Crit Care Med. 2013 Jun 15;187(12):1287-93. doi: 10.1164/rccm.201301-0036CP.
- Background: PubMed 22988082Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17537-42. doi: 10.1073/pnas.1202870109. Epub 2012 Sep 17.
- Background: PubMed 24192057Kleinnijenhuis J, Quintin J, Preijers F, Benn CS, Joosten LA, Jacobs C, van Loenhout J, Xavier RJ, Aaby P, van der Meer JW, van Crevel R, Netea MG. Long-lasting effects of BCG vaccination on both heterologous Th1/Th17 responses and innate trained immunity. J Innate Immun. 2014;6(2):152-8. doi: 10.1159/000355628. Epub 2013 Oct 30.
- Derived from this study: PubMed 25883989Hamers LA, Kox M, Arts RJ, Blok B, Leentjens J, Netea MG, Pickkers P. Gamma-irradiated bacille Calmette-Guerin vaccination does not modulate the innate immune response during experimental human endotoxemia in adult males. J Immunol Res. 2015;2015:261864. doi: 10.1155/2015/261864. Epub 2015 Mar 26.
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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.
Peter Pickkers, Prof. study director
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing BCG vaccine and Lipopolysaccharide (LPS) E. Coli 1 ng/kg intravenously in people with Sepsis, run by Radboud University Medical Center at 1 site in Netherlands.
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 4 inclusion and 20 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 13 May 2015. 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 Netherlands. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
To determine the effects of γ-irradiated BCG-vaccination on the in vivo innate immune responses induced by human endotoxemia. (time frame: Several time points within 1 month after vaccination). 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 NCT02085590, which also lists 5 linked publications.
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 13 May 2015.