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What is the purpose of this trial?

Tuberculosis (also known as TB) is a disease caused by a bacterium (Mycobacterium tuberculosis). TB disease remains one of the top 10 causes of death worldwide. BCG (Bacille Calmette-Guérin) is the only vaccine currently licenced for use against TB, but it is not always protective.

It is difficult to develop new TB vaccines, as it is not easy to determine which ones will work well and which will not. In vaccine studies against other diseases, such as influenza and malaria, it is possible to experimentally infect volunteers with the disease in question to see if the vaccine being studied is effective. This is called a “challenge” and is possible where the disease being studied is self-limiting or where safe, effective and short treatment regimens exist. This is not the case with TB, which requires a minimum of 6 months of treatment with multiple medications.

We have developed a ‘challenge model’, where we give the BCG as an infectious agent to healthy volunteers as a mimic for TB infection. The bacteria in the vaccine are still alive but, because they are weakened, they do not cause disease in healthy individuals. However, as the BCG and TB bacteria are similar, studying how the body’s immune system responds to and “fights off” BCG can give us important information about how well a new TB vaccine might work.

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Am I eligible to participate?

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FAQ

What is BCG?

BCG is a strain of the bacterium that causes TB in cattle. It is a live vaccine, meaning the bacteria in the vaccine are still alive but are weakened so that they do not cause TB disease, but do improve the body’s immune response against TB.

Is BCG safe?

BCG is one of the most widely used vaccines in the world. Several billion people have been given the vaccine over the past 100 years and no serious side effects have been seen in healthy people. BCG is usually given as an intradermal injection and is not licensed as an aerosol, although it has been given as an aerosol in three previous trials in the 1960s and 70s as well as in our group’s trial (TB041 and TB043). The TB041 study has now finished with no safety concerns. TB043 study is ongoing and we are continuing to collect safety data. The main purpose of this third study is to ensure the safety of giving inhaled BCG to people who have previously been vaccinated with BCG. We are also collecting information about the body’s immune response to BCG.

What does the trial involve?

Overall, the study will recruit 12 people into 4 groups.

The first group will contain 3 volunteers who will receive a low dose of inhaled BCG. The following groups will receive incrementally higher doses of BCG until we reach the doses given in our previous studies. All volunteers will have a bronchoscopy 14 days after inhaling the BCG (Day 0 challenge). There will be two short follow up visits between Day 0 and bronchoscopy visit, with further 4 full study visits after. Up to four brief additional visits for SARS-CoV-2 tests may be required. Volunteers will be in trial participation for up to 6 months.

For full details of all visits, please read the participant information sheet.

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 Figure 1. Trial timeline. SARS-CoV-2 tests may be performed 2 days prior to D0, bronchoscopy and any Induced Sputum procedures.

 

Is there any reimbursement for the trial?

Participants are reimbursed up to £750 for their time, travel and inconvenience. Full details of the reimbursement can be found in the participant information sheet.

 

What are the advantages of taking part?

You will not necessarily gain any direct benefit from the study, however, during pre-study assessment you will get information about your general health including results from a medical examination, blood tests, urine tests, chest x-ray and lung function measurement. You may also get information about your health from the bronchoscopy. However, these assessments are not carried out for diagnostic purposes and should not be considered a substitute for a doctor’s visit. Information gained from this study may aid in the development of a more effective vaccination programme to prevent TB worldwide.

 

Are there any risks from taking part in the trial?

The main risks and side effects of the proposed trial procedures are listed here.

  • Blood samples: drawing blood may cause slight pain and occasionally bruising
  • Aerosol inhalation of BCG: Inhalation is a safe route for giving medicines. 31 volunteers inhaled the BCG in our TB041 study, with all side effects seen lasting a short duration only. Potential local side effects could include sore throat, tickly throat, shortness of breath, wheezing, chest pain, chest tightness, dry cough or cough with phlegm. Side effects could occur within the first few days of BCG infection and/or a week or two later. A doctor will be available throughout the vaccination and the clinic room is equipped with oxygen and medications to treat any other symptoms.
  • Bronchoscopy: This is a widely used routine medical procedure for diagnosing and treating illnesses of the lungs and airways and in research studies involving healthy volunteers. It will be performed in a dedicated NHS bronchoscopy unit at the Oxford University Hospitals NHS Foundation Trust by a consultant respiratory physician, who will discuss the risks with you before the procedure. For more information about this, please refer to the participant information sheet.

You will be monitored in clinic following aerosol BCG inhalation for any reaction.

If you experience unexpected events or become concerned during the study you can call the emergency contact number given to you at enrolment. A qualified study doctor is available at all times on this number.

Please refer to the participant information sheet for full details of procedures and potential risks.

 

What will happen if I don't want to carry on with the study?

Participation is voluntary and you are free to withdraw at any time. If you withdraw we would not usually perform any more research procedures, although occasionally we might need to offer you a follow up visit, for example, to check a blood result. With your permission we would like to store the samples that we had already collected but if you did not want this we would discard them. If you choose to withdraw from the study, your standard medical care will not be affected.

For more details about the trial, see the participant information sheet.

If you are interested in taking part please email: vaccinetrials@ndm.ox.ac.uk