Influenza Virus InfectionPhase 2/3NCT02114255
Effects of BCG on Influenza Induced Immune Response
A Phase 2/3 study testing BCG in people with Influenza Virus Infection and Trained Immunity, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
In the present study, the investigators want to investigate whether prior BCG-vaccination improves the efficacy of influenza ("the flu") vaccination in young and/or old healthy volunteers and consequently could protect against influenza virus infection. 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
- Influenza Virus Infection, Trained Immunity
- What is being tested?
- BCG
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2014to Sep 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
- Age ≥18 and ≤35 yrs
- Male
- Healthy
Who cannot join
- History of influenza vaccination within the year prior to study entry
- History of BCG vaccination within 5 years prior to study entry
- History of Mantoux testing within the year prior to study entry
- Vaccination other than BCG or influenza, within 3 months prior to study or within study period
- Medical history of any disease associated with immune deficiency
- Clinically significant acute illness, including infections, within 4 weeks before vaccination
Show all 11Show fewer
- Participation in a drug trial or donation of blood 3 months prior to study entry
- Use of recreational drugs within 21 days prior to experiment day
- Recent hospital admission or surgery with general anaesthesia (<3 months)
- Known chronic kidney or liver disease
- Latent or active tuberculosis infection
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6525 GA
About this study
Official title: The Effects of BCG-vaccination on the Immune Response Induced by Influenza-vaccination in Healthy Volunteers. A Pilot Proof-of-principle Study.
In the present study, the investigators want to investigate whether prior BCG-vaccination improves the efficacy of influenza ("the flu") vaccination in young and/or old healthy volunteers and consequently could protect against influenza virus infection.
Read the detailed description
Influenza virus infection leads to millions of cases of severe illnesses worldwide and up to an estimated 500.000 deaths annually. The potential for the sudden emergence of pandemic influenza strains represents an incessant threat on even a larger scale. seasonal influenza vaccination is the backbone of influenza management. However, antibodies generated by vaccination, most often do not effectively neutralize emergent strains due to the high mutation rate of the influenza viral genome. In addition, although vaccination is effective in up to 85% of healthy adults, only 40-60% of the elderly are able to mount an protective antibody response due to an agerelated decline in immune function (so-called immunoscenescence). As a result, the protective effects of influenza vaccination are limited, and strategies to improve host immune defenses against influenza virus infection per se, and following influenza vaccination, are highly warranted.
It is suggested that prior vaccination with Bacille Calmette-Guérin (BCG) could enhance resistance to other infectious diseases in addition to protection to tuberculosis (TBC) and, in mice, protection of prior BCGvaccination against influenza infection was demonstrated long ago. However, only recently substantial evidence for these nonspecific beneficial effects of BCG-vaccination in humans has been provided by several randomized clinical trials. Considering these potentiating effects of BCG-vaccination, it could be a viable strategy to improve efficacy of influenza vaccination, and/or enhance immune defenses against influenza virus infection per se. If so, this would have an enormous impact on clinical practice.
- Conditions
- Influenza Virus Infection, Trained Immunity
- Being tested
- Placebo, BCG
- Keywords
- Influenza, Trained immunity, BCG
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Administration of 0.9% NaCl.
BCGBiological
Vaccination with the live attenuated BCG vaccine.
| Study group | Role | What they receive |
|---|---|---|
| BCG vaccination | Experimental | BCG vaccination Receives: Biological: BCG |
| NaCl 0.9% | Placebo comparator | administration of NaCl 0.9%. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in influenza antibody titres between BCG-vaccinated subjects and subjects in the control group
Measured: Day 14, day 21, day 28, day 42 (±2 days)
Difference in Thrombocyte function between BCG-vaccinated subjects and subjects in the control group
Measured: Day 0, day 14, day 21, day 28, day 42 (±2 days)
Secondary outcomes (7)
Proportion of participants in each group who achieved seroprotection (defined by antibody titre ≥1:40).
Measured: day 21, day 28, day 42 (±2 days)
Proportion of participants in each group who achieved seroconversion (defined by a ≥4-fold rise in antibody titre).
Measured: day 21, day 28, day 42 (±2 days)
IFN-gamma/IL-10 production of leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Measured: Day 0, day 14, day 28, day 42 (±2 days)
Production of Type 1 IFNs, IL-17 and IL-22 by leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Measured: Day 0, day 14, day 28, day 42 (±2 days)
Production of other inflammatory mediators (including TNFα, IL-1β, IFN-gamma, IL-10, IL-17, IL-22) by leukocytes ex vivo stimulated with different not-related stimuli (including m. tuberculosis, s. aureus, c. albicans, and inactivated influenza).
Measured: Day 0, day 21, day 28, day 42 (±2 days)
Inflammatory transcriptional pathways (by use of qPCR/microarrays) .
Measured: Day 0, day 14, day 28, day 42 (±2 days)
Granzyme B production of leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Measured: Day 0, day 14, day 28, day 42 (±2 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza Virus InfectionStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mihai Netea, PhD, Principal investigator, Radboud University Nijmegen Medical Centre, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02114255
- Sponsor's protocol ID
- BCG_influenza
- Status last verified
- Nov 2015
- First submitted
- 10 Mar 2014
- Last updated
- 10 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of BCG-vaccination on the Immune Response Induced by Influenza-vaccination in Healthy Volunteers. A Pilot Proof-of-principle Study.
- ClinicalTrials.gov ID
- NCT02114255
- Acronym / sponsor ID
- BCG_influenza
- Conditions
- Influenza Virus Infection, Trained Immunity
- Keywords
- Influenza, Trained immunity, BCG
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 15 Apr 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, the investigators want to investigate whether prior BCG-vaccination improves the efficacy of influenza ("the flu") vaccination in young and/or old healthy volunteers and consequently could protect against influenza virus infection.
Detailed description
Influenza virus infection leads to millions of cases of severe illnesses worldwide and up to an estimated 500.000 deaths annually. The potential for the sudden emergence of pandemic influenza strains represents an incessant threat on even a larger scale. seasonal influenza vaccination is the backbone of influenza management. However, antibodies generated by vaccination, most often do not effectively neutralize emergent strains due to the high mutation rate of the influenza viral genome. In addition, although vaccination is effective in up to 85% of healthy adults, only 40-60% of the elderly are able to mount an protective antibody response due to an agerelated decline in immune function (so-called immunoscenescence). As a result, the protective effects of influenza vaccination are limited, and strategies to improve host immune defenses against influenza virus infection per se, and following influenza vaccination, are highly warranted.
It is suggested that prior vaccination with Bacille Calmette-Guérin (BCG) could enhance resistance to other infectious diseases in addition to protection to tuberculosis (TBC) and, in mice, protection of prior BCGvaccination against influenza infection was demonstrated long ago. However, only recently substantial evidence for these nonspecific beneficial effects of BCG-vaccination in humans has been provided by several randomized clinical trials. Considering these potentiating effects of BCG-vaccination, it could be a viable strategy to improve efficacy of influenza vaccination, and/or enhance immune defenses against influenza virus infection per se. If so, this would have an enormous impact on clinical practice.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BCG vaccination | Experimental | Biological: BCGBCG vaccination |
| NaCl 0.9% | Placebo comparator | Other: Placeboadministration of NaCl 0.9%. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Age ≥18 and ≤35 yrs
- Male
- Healthy
Key exclusion criteria (11 listed)
- History of influenza vaccination within the year prior to study entry
- History of BCG vaccination within 5 years prior to study entry
- History of Mantoux testing within the year prior to study entry
- Vaccination other than BCG or influenza, within 3 months prior to study or within study period
- Medical history of any disease associated with immune deficiency
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 |
|---|---|---|
| PlaceboAdministration of 0.9% NaCl. | Other | NaCl 0.9% |
| BCGVaccination with the live attenuated BCG vaccine. | Biological | BCG vaccination |
Primary outcome
Difference in influenza antibody titres between BCG-vaccinated subjects and subjects in the control group
Time frame: Day 14, day 21, day 28, day 42 (±2 days)
Difference in Thrombocyte function between BCG-vaccinated subjects and subjects in the control group
Time frame: Day 0, day 14, day 21, day 28, day 42 (±2 days)
7 secondary outcomes
Proportion of participants in each group who achieved seroprotection (defined by antibody titre ≥1:40).
Time frame: day 21, day 28, day 42 (±2 days)
Proportion of participants in each group who achieved seroconversion (defined by a ≥4-fold rise in antibody titre).
Time frame: day 21, day 28, day 42 (±2 days)
IFN-gamma/IL-10 production of leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Time frame: Day 0, day 14, day 28, day 42 (±2 days)
Production of Type 1 IFNs, IL-17 and IL-22 by leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Time frame: Day 0, day 14, day 28, day 42 (±2 days)
Production of other inflammatory mediators (including TNFα, IL-1β, IFN-gamma, IL-10, IL-17, IL-22) by leukocytes ex vivo stimulated with different not-related stimuli (including m. tuberculosis, s. aureus, c. albicans, and inactivated influenza).
Time frame: Day 0, day 21, day 28, day 42 (±2 days)
Inflammatory transcriptional pathways (by use of qPCR/microarrays) .
Time frame: Day 0, day 14, day 28, day 42 (±2 days)
Granzyme B production of leukocytes ex vivo stimulated with inactivated/live influenza virus (0.1ug HA/ml).
Time frame: Day 0, day 14, day 28, day 42 (±2 days)
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 10 Nov 2015.
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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.
Mihai Netea, PhD principal investigator
Radboud University Nijmegen Medical Centre, The Netherlands
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 in people with Influenza Virus Infection and Trained Immunity, 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 3 inclusion and 11 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 10 Nov 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?
Difference in influenza antibody titres between BCG-vaccinated subjects and subjects in the control group (time frame: Day 14, day 21, day 28, day 42 (±2 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Nov 2015.