A Phase 4 interventional study of Bacille Calmette-Guerin and BCG solvent in Innate Immunity and Bacille Calmette-Guérin, sponsored by Bandim Health Project. Completed at 1 site in Guinea-Bissau. Open to participants aged 50 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-04-26.
Sponsored by Bandim Health Project · Phase 4, Interventional, and Basic science
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.
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.
Bandim Health Project is the lead sponsor of 59 studies on the registry; 5 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Intervention arm, these participants will receive BCG vaccination.
Biological: Bacille Calmette-Guerin
The placebo arm will receive BCG solvent.
Biological: BCG solvent
Vaccine against tuberculosis
Also known as: BCG
Simple solvent
Also known as: Diluent
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.
Time frame: 2 weeks
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.
Time frame: 3 months
Difference in percentage before and after BCG vaccination of a specific marker on a specific gene (e.g. H3K4me3 on TNF (tumor necrosis factor) gene).
Measurement of change in epigenetics after intervention, compared to before intervention.
Time frame: 2 weeks and 3 months after inclusion
Consultation
The amount of consultations in the 3 months we follow the participants. To see if there is a difference between the 2 interventions.
Time frame: 3 months
Medication use
The amount of medication use in the 3 months we follow the participants. To see if there is a difference between the 2 interventions.
Time frame: 3 months
This study is completed, as verified in Apr 2021. You cannot join it, but the record below documents what was studied.
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