Innate ImmunityPhase 4NCT02953327
Testing if BCG (Bacille Calmette-Guérin) Vaccination Can Induce Innate Immune Training in Adult People Above 50 Years of Age in Guinea-Bissau
A Phase 4 study testing Bacille Calmette-Guerin and BCG solvent in people with Innate Immunity and Bacille Calmette-Guérin, run by Bandim Health Project at 1 site in Guinea-Bissau.
Trial summary
The propose is to test innate immune training in a pilot study of 40 adults >50 years of age people in Guinea-Bissau. The hypothesis is that BCG vaccination will be associated with increased innate immune training measured as increased cytokine release after in vitro Peripheral Blood Mononuclear Cells (PBMC)… Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Innate Immunity, Bacille Calmette-Guérin
- What is being tested?
- Bacille Calmette-Guerin and BCG solvent
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteGuinea-Bissau
- Study dates
- 1 Feb 2017to 15 Jun 2020
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- adults above 50 years of age
Who cannot join
- Participants who received BCG in the last 10 years will be excluded.
- Adults who were mild to severe ill in the last 2 week will be excluded.
- Adults how have been in contact with the health system (hospital or health center) for the last 14 days will be excluded.
- People that show signs of overt disease will not be enrolled, but treated according to local standards and invited back when better.
- If the person has any sign of TB, they will excluded and be referred to the TB clinic for further investigations and treatment.
- All participants will be tested for HIV. If the test is positive, they will have an opportunity to talk with a psychologist, and we will refer them to the HIV clinic. HIV positive persons will be excluded from the present study.
Trial locations and contacts
1 site in 1 country.
About this study
The propose is to test innate immune training in a pilot study of 40 adults >50 years of age people in Guinea-Bissau. The hypothesis is that BCG vaccination will be associated with increased innate immune training measured as increased cytokine release after in vitro Peripheral Blood Mononuclear Cells (PBMC) stimulation with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae.
Read the detailed description
BCG was developed as a vaccine against tuberculosis (TB), but many studies have now confirmed its ability to induce potent protection against other infectious diseases in children. It has recently been shown that this may be linked to increased response of the innate immune system to several non-specific pathogens after BCG exposure, so called 'innate immune training'. This training ability of BCG has been shown for children and young adults. However, to our knowledge, no studies on the ability of BCG to induce innate immune training in adults >50 years of age have been conducted. Immune training in elderly is of interest since with increasing age, the immune system gets weaker, and responds less adequately to a number of infections, for instance influenza. Thus, if BCG is able to stimulate the innate immune system in mature adults as well, it could potentially reduce the risk of serious infections in elderly.
To investigate whether BCG has innate immune training effects in mature adults, a randomized pilot study of 40 adults >50 years of age in Guinea-Bissau will be conducted. The Bandim Health Project has conducted multiple large-scale RCT's and demographic surveillance. HIV negative adults >50 years of age in a recent HIV survey are eligible for the present study. They will be checked for clinical signs of TB and an HIV test will be preformed before enrolment. Exclusion criteria are BCG vaccination within the last 10 years, illness within the last 14 days, clinical signs of active TB, and/or a positive HIV test. Those who are overtly ill will be treated or referred to hospital if needed. Those with signs of TB will be referred to the TB hospital for further examinations. Those who have become HIV positive since they were tested in the survey will receive immediate counselling and be referred to the HIV clinic.
Participants will be randomized to either BCG vaccination or placebo. To test the innate immune system blood will be withdraw 3 times: before the intervention, 2 weeks and 3 months after the intervention. There is a maximum of 10 ml blood each time, plus 3 ml the first time for the Quantiferon. This is a small volume, with a maximum of 33 ml and should not cause any problems for participants. Quantiferon results will be used as a baseline to test if participants are sensitized to mycobacterium Tuberculosis. In the blood, the innate immune training effects of BCG we will investigated by studying how the immune cells respond when they are stimulated with bacteria or other pathogens, which can cause serious infections. Provided that BCG shows induced innate immune training in adults >50 years of age, a large randomized control trial will follow to see if BCG vaccination reduces the number of acute infections in adults >50 years of age in Guinea-Bissau.
- Conditions
- Innate Immunity, Bacille Calmette-Guérin
- Being tested
- Bacille Calmette-Guerin, BCG solvent
- Keywords
- Non-Specific Effect of Vaccine, Middle aged, Immunity, heterologous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bacille Calmette-GuerinBiological
Also called BCG
Vaccine against tuberculosis
BCG solventBiological
Also called Diluent
Simple solvent
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Intervention arm, these participants will receive BCG vaccination. Receives: Biological: Bacille Calmette-Guerin |
| Placebo arm | Placebo comparator | The placebo arm will receive BCG solvent. Receives: Biological: BCG solvent |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cytokine level at 2 weeks compared to the baseline
Before intervention and 2 weeks after, blood will be withdrawn and the PBMC will be isolated. In vitro stimulation of the PBMC will be done with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae for 24h and 7 days. After this the cytokine levels will be measured.
Measured: 2 weeks
Secondary outcomes (1)
Change in cytokine level at 3 months compared to the baseline
Before intervention and 3 months after the intervention, blood will be withdrawn and the PBMC will be isolated. In vitro stimulation of the PBMC will be done with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae for 24h and 7 days. After this the cytokine levels will be measured. The cytokine level 3 months after intervention is the secondary outcome.
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 posted2 Nov 2016 (estimated)
- Study start1 Feb 2017
- Primary completion15 Jun 2017
- Study completion15 Jun 2020
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 Innate ImmunityStudies of the same condition, open and under way.
- 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
- Single blind
- Who is masked
- Care provider
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bandim Health Project
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02953327
- Sponsor's protocol ID
- BCGadult
- Status last verified
- Apr 2021
- First submitted
- 21 Oct 2016
- Last updated
- 26 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Berendsen MLT, Bles P, de Bree LCJ, Jensen KJ, Jensen CC, Wejse C, Mendes DV, Netea MG, Benn CS. Bacillus Calmette-Guerin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau. Vaccine. 2024 Dec 2;42(26):126439. doi: 10.1016/j.vaccine.2024.126439. Epub 2024 Oct 17.
PubMed 39423450
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing if BCG (Bacille Calmette-Guérin) Vaccination Can Induce Innate Immune Training in Adult People Above 50 Years of Age in Guinea-Bissau
- ClinicalTrials.gov ID
- NCT02953327
- Acronym / sponsor ID
- BCGadult
- Conditions
- Innate Immunity, Bacille Calmette-Guérin
- Keywords
- Non-Specific Effect of Vaccine, Middle aged, Immunity, heterologous
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Bandim Health ProjectUniversity, hospital or other
- Collaborators
- Radboud University Medical Center
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 15 Jun 2017 (actual)
- Study completion
- 15 Jun 2020 (actual)
- First posted
- 2 Nov 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.
The propose is to test innate immune training in a pilot study of 40 adults >50 years of age people in Guinea-Bissau. The hypothesis is that BCG vaccination will be associated with increased innate immune training measured as increased cytokine release after in vitro Peripheral Blood Mononuclear Cells (PBMC) stimulation with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae.
Detailed description
BCG was developed as a vaccine against tuberculosis (TB), but many studies have now confirmed its ability to induce potent protection against other infectious diseases in children. It has recently been shown that this may be linked to increased response of the innate immune system to several non-specific pathogens after BCG exposure, so called 'innate immune training'. This training ability of BCG has been shown for children and young adults. However, to our knowledge, no studies on the ability of BCG to induce innate immune training in adults >50 years of age have been conducted. Immune training in elderly is of interest since with increasing age, the immune system gets weaker, and responds less adequately to a number of infections, for instance influenza. Thus, if BCG is able to stimulate the innate immune system in mature adults as well, it could potentially reduce the risk of serious infections in elderly.
To investigate whether BCG has innate immune training effects in mature adults, a randomized pilot study of 40 adults >50 years of age in Guinea-Bissau will be conducted. The Bandim Health Project has conducted multiple large-scale RCT's and demographic surveillance. HIV negative adults >50 years of age in a recent HIV survey are eligible for the present study. They will be checked for clinical signs of TB and an HIV test will be preformed before enrolment. Exclusion criteria are BCG vaccination within the last 10 years, illness within the last 14 days, clinical signs of active TB, and/or a positive HIV test. Those who are overtly ill will be treated or referred to hospital if needed. Those with signs of TB will be referred to the TB hospital for further examinations. Those who have become HIV positive since they were tested in the survey will receive immediate counselling and be referred to the HIV clinic.
Participants will be randomized to either BCG vaccination or placebo. To test the innate immune system blood will be withdraw 3 times: before the intervention, 2 weeks and 3 months after the intervention. There is a maximum of 10 ml blood each time, plus 3 ml the first time for the Quantiferon. This is a small volume, with a maximum of 33 ml and should not cause any problems for participants. Quantiferon results will be used as a baseline to test if participants are sensitized to mycobacterium Tuberculosis. In the blood, the innate immune training effects of BCG we will investigated by studying how the immune cells respond when they are stimulated with bacteria or other pathogens, which can cause serious infections. Provided that BCG shows induced innate immune training in adults >50 years of age, a large randomized control trial will follow to see if BCG vaccination reduces the number of acute infections in adults >50 years of age in Guinea-Bissau.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Biological: Bacille Calmette-GuerinIntervention arm, these participants will receive BCG vaccination. |
| Placebo arm | Placebo comparator | Biological: BCG solventThe placebo arm will receive BCG solvent. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adults above 50 years of age
Key exclusion criteria (6 listed)
- Participants who received BCG in the last 10 years will be excluded.
- Adults who were mild to severe ill in the last 2 week will be excluded.
- Adults how have been in contact with the health system (hospital or health center) for the last 14 days will be excluded.
- People that show signs of overt disease will not be enrolled, but treated according to local standards and invited back when better.
- If the person has any sign of TB, they will excluded and be referred to the TB clinic for further investigations and treatment.
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 |
|---|---|---|
| Bacille Calmette-GuerinAlso: BCGVaccine against tuberculosis | Biological | Intervention arm |
| BCG solventAlso: DiluentSimple solvent | Biological | Placebo arm |
Primary outcome
Change in cytokine level at 2 weeks compared to the baseline
Time frame: 2 weeks
Before intervention and 2 weeks after, blood will be withdrawn and the PBMC will be isolated. In vitro stimulation of the PBMC will be done with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae for 24h and 7 days. After this the cytokine levels will be measured.
1 secondary outcome
Change in cytokine level at 3 months compared to the baseline
Time frame: 3 months
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 26 Apr 2021.
- Derived from this study: PubMed 39423450Berendsen MLT, Bles P, de Bree LCJ, Jensen KJ, Jensen CC, Wejse C, Mendes DV, Netea MG, Benn CS. Bacillus Calmette-Guerin vaccination induces a trained innate immunity phenotype in adults over 50 years of age: A randomized trial in Guinea-Bissau. Vaccine. 2024 Dec 2;42(26):126439. doi: 10.1016/j.vaccine.2024.126439. Epub 2024 Oct 17.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Bacille Calmette-Guerin and BCG solvent in people with Innate Immunity and Bacille Calmette-Guérin, run by Bandim Health Project at 1 site in Guinea-Bissau.
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 6 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 26 Apr 2021. 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 Guinea-Bissau. 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 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?
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?
Change in cytokine level at 2 weeks compared to the baseline (time frame: 2 weeks). 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 NCT02953327, 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 26 Apr 2021.