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Testing if BCG (Bacille Calmette-Guérin) Vaccination Can Induce Innate Immune Training in Adult People Above 50 Years of Age in Guinea-Bissau

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ClinicalTrials.gov Identifier: NCT02953327
Recruitment Status : Unknown
Verified January 2017 by Bandim Health Project.
Recruitment status was:  Recruiting
First Posted : November 2, 2016
Last Update Posted : February 1, 2017
Sponsor:
Collaborator:
Radboud University
Information provided by (Responsible Party):
Bandim Health Project

Brief 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) stimulation with e.g. Mycobacterium Tuberculosis, Staphylococcus Aureus, Candida Albicans and Streptococcus Pneumoniae.

Condition or disease Intervention/treatment Phase
Innate Immunity Bacille Calmette-Guérin Biological: Bacille Calmette-Guerin Biological: BCG solvent Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Care Provider)
Primary Purpose: Basic Science
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
Study Start Date : January 2017
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : December 2017

Arm Intervention/treatment
Experimental: Intervention arm
Intervention arm, these participants will receive BCG vaccination.
Biological: Bacille Calmette-Guerin
Other Name: BCG

Placebo Comparator: Placebo arm
The placebo arm will receive BCG solvent.
Biological: BCG solvent
Other Name: Diluent




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Change in cytokine level at 3 months compared to the baseline [ Time Frame: 3 months ]
    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.


Other Outcome Measures:
  1. 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). [ Time Frame: 2 weeks and 3 months after inclusion ]
    Measurement of change in epigenetics after intervention, compared to before intervention.

  2. Consultation [ Time Frame: 3 months ]
    The amount of consultations in the 3 months we follow the participants. To see if there is a difference between the 2 interventions.

  3. Medication use [ Time Frame: 3 months ]
    The amount of medication use in the 3 months we follow the participants. To see if there is a difference between the 2 interventions.



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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • adults above 50 years of age

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02953327


Contacts
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Contact: Pauli Bles, MSc 00245 955106914 pabl@ssi.dk
Contact: Christine Benn, Professor cb@ssi.dk

Locations
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Guinea-Bissau
Bandim Health Project Recruiting
Bissau, Bissau Codex, Guinea-Bissau, 1004
Contact: Christine Benn, DMSc       cb@ssi.dk   
Contact: Peter Aaby, DMSc       p.aaby@bandim.org   
Principal Investigator: Christine Benn, DMSc         
Sponsors and Collaborators
Bandim Health Project
Radboud University

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Responsible Party: Bandim Health Project
ClinicalTrials.gov Identifier: NCT02953327     History of Changes
Other Study ID Numbers: BCGadult
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: February 1, 2017
Last Verified: January 2017

Keywords provided by Bandim Health Project:
Non-Specific Effect of Vaccine
Middle aged
Immunity, heterologous

Additional relevant MeSH terms:
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Vaccines
Immunologic Factors
Physiological Effects of Drugs