Whooping CoughPhase 4NCT02771782
Influence of BCG on TDaP-IPV Vaccination
A Phase 4 study testing BCG vaccine (SSI) and TDaP-IPV vaccine in people with Whooping Cough, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
This study has three purposes: To investigate whether the immune response to pertussis is increased when TDaP-IPV is given together with BCG vaccine, compared to when it is given alone. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Whooping Cough
- What is being tested?
- BCG vaccine (SSI) and TDaP-IPV vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2015to Apr 2017
- Phase
- Phase 4
- 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 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy females
Who cannot join
- systemic medication use other than oral contraceptive drugs
- history of disease resulting in immunodeficiency
- previous vaccination with BCG
- pregnancy
- allergy to neomycin or polymyxin
- known previous allergic reaction to vaccination with diphteria, tetanus, pertussis or polio vaccines
- One of following phenomena after previous vaccination with pertussis containing antigens: Fever >40 °C within 48 hours after vaccination, hypotonous-hyporesponsiveness episode within 48 hours after vaccination, convulsions with or without fever within 3 days after vaccination
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Influence of BCG Vaccine as a Booster TDaP-IPV Vaccination: an Explorative Study
This study has three purposes:
To investigate whether the immune response to pertussis is increased when TDaP-IPV is given together with BCG vaccine, compared to when it is given alone.
To investigate whether BCG vaccination modulates the immune response to non vaccine target antigens (i.e., antigens/pathogens not used in the vaccine itself).
To investigate whether TDaP-IPV vaccination modulates the immune response to non vaccine target antigens.
Read the detailed description
Rationale: The Bacillus Calmette-Guerin (BCG) vaccine not only protects against Mycobacterium tuberculosis, but has also been shown to reduce morbidity and mortality caused by non-related infections. This effect is likely due to non-specific immunomodulatory effects, at least in part on the innate immune system. Additionally, BCG has been shown to improve immunogenicity of other vaccinations. In contrast, whilst the diphtheria-tetanus-pertussis (DTP) combination vaccine protects against infection with Bordetella pertussis, Clostridium tetani and Corynebacterium diphtheria, it has also been associated with increased mortality due to unrelated infections, particularly in girls in high-mortality countries.
Although widespread DTP vaccination has initially reduced pertussis mortality, the disease has persisted and recently resurged in a number of countries with highly vaccinated populations, including the Netherlands. This has been partially attributed to the switch from a whole-cell vaccine (which is still being used in low-income countries) to a more defined acellular pertussis vaccine, which only protects for a limited period (5-8 years). Strategies to improve the efficacy of pertussis vaccination are therefore urgently required.
As the BCG vaccine has already been used to improve the immunogenicity of other vaccines, the investigators hypothesize that BCG vaccination before or at the same time of DTP vaccination increases the immunogenicity of the DTP vaccine in terms of antibody and T-cell responses to pertussis. Moreover, the investigators aim to assess the effect of DTP vaccination on the known long-term beneficial non-specific effects of BCG on non-mycobacterial infections.
Objective: To examine the effect of BCG as an adjuvant on DTP vaccination, and to investigate the non-specific training effects of BCG and DTP, alone and in combination, on the innate immune system.
Study population: Healthy adult volunteers.
Main study parameters: Comparison of pertussis-specific antibody and T-cell responses, as well as gene transcription between BCG, TDaP-IPV and BCG+TDaP-IPV vaccinated groups. Comparison of cytokine responses to unrelated antigens and/or pathogens before and after BCG, TDaP-IPV or BCG+TDaP-IPV vaccination.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no direct benefit to the study participants but these results will potentially lead to novel strategies to optimize vaccinations. The risks for participants are negligible, with the only expected risks being minor side-effects from vaccination and local hematoma forming at the site of venepuncture. This will be minimized by the performance of these procedures by experienced personnel.
- Conditions
- Whooping Cough
- Being tested
- BCG vaccine (SSI), TDaP-IPV vaccine
- Keywords
- BCG, TDaP-IPV, DPT Vaccine
- Medical subject headings
- Whooping Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG vaccine (SSI)Biological
TDaP-IPV vaccineBiological
| Study group | Role | What they receive |
|---|---|---|
| BCG | Experimental | Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal Receives: Biological: BCG vaccine (SSI) |
| TDaP-IPV | Experimental | Subjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular Receives: Biological: TDaP-IPV vaccine |
| BCG+TDaP-IPV | Experimental | Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously Receives: Biological: BCG vaccine (SSI); Biological: TDaP-IPV vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antibody response to TDaP-IPV
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Measured: 2 weeks
Antibody response to TDaP-IPV
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Measured: 3 months
Antibody response to TDaP-IPV
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Measured: 1 year
T-cell response to TDaP-IPV
T-cell responses will be measured by FACS
Measured: 2 weeks
T-cell response to TDaP-IPV
T-cell responses will be measured by FACS
Measured: 3 months
T-cell response to TDaP-IPV
T-cell responses will be measured by FACS
Measured: 1 year
PBMC cytokine response to pertussis related antigens
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
Measured: 2 weeks
PBMC cytokine response to pertussis related antigens
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
Measured: 3 months
PBMC cytokine response to pertussis related antigens
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
Measured: 1 year
B-cell phenotype analysis
pertussis specific B-cells will be analyzed by FACS
Measured: 2 weeks
B-cell phenotype analysis
pertussis specific B-cells will be analyzed by FACS
Measured: 3 months
B-cell phenotype analysis
pertussis specific B-cells will be analyzed by FACS
Measured: 1 year
Secondary outcomes (13)
PBMC responses to heterologous antigens
PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured
Measured: 1 day
PBMC responses to heterologous antigens
PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured
Measured: 4 days
PBMC responses to heterologous antigens
PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured
Measured: 2 weeks
PBMC responses to heterologous antigens
PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured
Measured: 3 months
PBMC responses to heterologous antigens
PBMCs will be stimulated with LPS, S. aureus, C.albicans, PHA, S.pneumoniae, zymosan. Responses on cytokine levels (IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g) and ROS production will be measured
Measured: 1 year
Transcriptional profile of PBMCs
Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
Measured: 1 day
Transcriptional profile of PBMCs
Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
Measured: 4 days
Transcriptional profile of PBMCs
Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
Measured: 2 weeks
Transcriptional profile of PBMCs
Transcriptional profile of PBMCs will be measured by RNAseq to assess for active gene transcription programs
Measured: 3 months
Epigenetic markers of monocytes
Levels of activating and inhibiting epigenetic marks will be assessed
Measured: 1 day
Epigenetic markers of monocytes
Levels of activating and inhibiting epigenetic marks will be assessed
Measured: 4 days
Epigenetic markers of monocytes
Levels of activating and inhibiting epigenetic marks will be assessed
Measured: 2 weeks
Epigenetic markers of monocytes
Levels of activating and inhibiting epigenetic marks will be assessed
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2016 (estimated)
- Study startJan 2015
- Primary completionJul 2016
- Study completionApr 2017 (estimated)
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 Whooping CoughStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern Denmark
- Responsible party
- Sponsor
- Investigators
- Mihai Netea, Prof. Dr., Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02771782
- Sponsor's protocol ID
- BCG-DKTP1
- Status last verified
- Apr 2016
- First submitted
- 22 Feb 2016
- Last updated
- 13 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Blok BA, de Bree LCJ, Diavatopoulos DA, Langereis JD, Joosten LAB, Aaby P, van Crevel R, Benn CS, Netea MG. Interacting, Nonspecific, Immunological Effects of Bacille Calmette-Guerin and Tetanus-diphtheria-pertussis Inactivated Polio Vaccinations: An Explorative, Randomized Trial. Clin Infect Dis. 2020 Jan 16;70(3):455-463. doi: 10.1093/cid/ciz246.
PubMed 30919883
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of BCG Vaccine as a Booster TDaP-IPV Vaccination: an Explorative Study
- ClinicalTrials.gov ID
- NCT02771782
- Acronym / sponsor ID
- BCG-DKTP1
- Conditions
- Whooping Cough
- Keywords
- BCG, TDaP-IPV, DPT Vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- University of Southern Denmark
- Study start
- Jan 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Apr 2017 (estimated)
- First posted
- 13 May 2016 (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.
This study has three purposes:
To investigate whether the immune response to pertussis is increased when TDaP-IPV is given together with BCG vaccine, compared to when it is given alone.
To investigate whether BCG vaccination modulates the immune response to non vaccine target antigens (i.e., antigens/pathogens not used in the vaccine itself).
To investigate whether TDaP-IPV vaccination modulates the immune response to non vaccine target antigens.
Detailed description
Rationale: The Bacillus Calmette-Guerin (BCG) vaccine not only protects against Mycobacterium tuberculosis, but has also been shown to reduce morbidity and mortality caused by non-related infections. This effect is likely due to non-specific immunomodulatory effects, at least in part on the innate immune system. Additionally, BCG has been shown to improve immunogenicity of other vaccinations. In contrast, whilst the diphtheria-tetanus-pertussis (DTP) combination vaccine protects against infection with Bordetella pertussis, Clostridium tetani and Corynebacterium diphtheria, it has also been associated with increased mortality due to unrelated infections, particularly in girls in high-mortality countries.
Although widespread DTP vaccination has initially reduced pertussis mortality, the disease has persisted and recently resurged in a number of countries with highly vaccinated populations, including the Netherlands. This has been partially attributed to the switch from a whole-cell vaccine (which is still being used in low-income countries) to a more defined acellular pertussis vaccine, which only protects for a limited period (5-8 years). Strategies to improve the efficacy of pertussis vaccination are therefore urgently required.
As the BCG vaccine has already been used to improve the immunogenicity of other vaccines, the investigators hypothesize that BCG vaccination before or at the same time of DTP vaccination increases the immunogenicity of the DTP vaccine in terms of antibody and T-cell responses to pertussis. Moreover, the investigators aim to assess the effect of DTP vaccination on the known long-term beneficial non-specific effects of BCG on non-mycobacterial infections.
Objective: To examine the effect of BCG as an adjuvant on DTP vaccination, and to investigate the non-specific training effects of BCG and DTP, alone and in combination, on the innate immune system.
Study population: Healthy adult volunteers.
Main study parameters: Comparison of pertussis-specific antibody and T-cell responses, as well as gene transcription between BCG, TDaP-IPV and BCG+TDaP-IPV vaccinated groups. Comparison of cytokine responses to unrelated antigens and/or pathogens before and after BCG, TDaP-IPV or BCG+TDaP-IPV vaccination.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: There is no direct benefit to the study participants but these results will potentially lead to novel strategies to optimize vaccinations. The risks for participants are negligible, with the only expected risks being minor side-effects from vaccination and local hematoma forming at the site of venepuncture. This will be minimized by the performance of these procedures by experienced personnel.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BCG | Experimental | Biological: BCG vaccine (SSI)Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal |
| TDaP-IPV | Experimental | Biological: TDaP-IPV vaccineSubjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular |
| BCG+TDaP-IPV | Experimental | Biological: BCG vaccine (SSI), Biological: TDaP-IPV vaccineSubjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- healthy females
Key exclusion criteria (7 listed)
- systemic medication use other than oral contraceptive drugs
- history of disease resulting in immunodeficiency
- previous vaccination with BCG
- pregnancy
- allergy to neomycin or polymyxin
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 vaccine (SSI) | Biological | BCG, BCG+TDaP-IPV |
| TDaP-IPV vaccine | Biological | BCG+TDaP-IPV, TDaP-IPV |
Primary outcome
Antibody response to TDaP-IPV
Time frame: 2 weeks
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Antibody response to TDaP-IPV
Time frame: 3 months
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Antibody response to TDaP-IPV
Time frame: 1 year
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
T-cell response to TDaP-IPV
Time frame: 2 weeks
T-cell responses will be measured by FACS
T-cell response to TDaP-IPV
Time frame: 3 months
T-cell responses will be measured by FACS
T-cell response to TDaP-IPV
Time frame: 1 year
T-cell responses will be measured by FACS
PBMC cytokine response to pertussis related antigens
Time frame: 2 weeks
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
PBMC cytokine response to pertussis related antigens
Time frame: 3 months
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
PBMC cytokine response to pertussis related antigens
Time frame: 1 year
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
B-cell phenotype analysis
Time frame: 2 weeks
pertussis specific B-cells will be analyzed by FACS
B-cell phenotype analysis
Time frame: 3 months
pertussis specific B-cells will be analyzed by FACS
B-cell phenotype analysis
Time frame: 1 year
pertussis specific B-cells will be analyzed by FACS
13 secondary outcomes
PBMC responses to heterologous antigens
Time frame: 1 day
PBMC responses to heterologous antigens
Time frame: 4 days
PBMC responses to heterologous antigens
Time frame: 2 weeks
PBMC responses to heterologous antigens
Time frame: 3 months
PBMC responses to heterologous antigens
Time frame: 1 year
Transcriptional profile of PBMCs
Time frame: 1 day
Transcriptional profile of PBMCs
Time frame: 4 days
Transcriptional profile of PBMCs
Time frame: 2 weeks
Transcriptional profile of PBMCs
Time frame: 3 months
Epigenetic markers of monocytes
Time frame: 1 day
Epigenetic markers of monocytes
Time frame: 4 days
Epigenetic markers of monocytes
Time frame: 2 weeks
Epigenetic markers of monocytes
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2016.
- Derived from this study: PubMed 30919883Blok BA, de Bree LCJ, Diavatopoulos DA, Langereis JD, Joosten LAB, Aaby P, van Crevel R, Benn CS, Netea MG. Interacting, Nonspecific, Immunological Effects of Bacille Calmette-Guerin and Tetanus-diphtheria-pertussis Inactivated Polio Vaccinations: An Explorative, Randomized Trial. Clin Infect Dis. 2020 Jan 16;70(3):455-463. doi: 10.1093/cid/ciz246.
- Individual participant dataSharing planned: Undecided
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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, Prof. Dr. principal investigator
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 4 study testing BCG vaccine (SSI) and TDaP-IPV vaccine in people with Whooping Cough, 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 1 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 13 Oct 2016. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Antibody response to TDaP-IPV (time frame: 2 weeks). The study lists 12 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 NCT02771782, 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 13 Oct 2016.