What is the purpose of this trial?
Tuberculosis (also known as TB) is a disease caused by a bacterium that continues to be a significant cause of death worldwide. BCG (Bacille Calmette-Guérin) is the only vaccine currently in use against TB. BCG has some effect against TB disease in childhood, but it is not good enough at protecting against disease in adulthood. We are working on developing booster vaccines that can be given after BCG immunisation in the hope of providing greater protection against TB. However, it is not easy to work out which vaccines work well and which do not. To help work this out, we have developed a ‘challenge model’ – this is where we give healthy volunteers an inhaled dose of BCG and see how their body reacts to the BCG. We know that Mycobacterium tuberculosis, the bacterium that causes TB, infects people by being breathed into the lungs, so an inhaled BCG ‘challenge’ may imitate TB infection. We hope that this will help improve our understanding of TB infection for future TB vaccine development.
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 90 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) with no serious side effects. The TB041 study is close to finishing but we are still collecting safety data. The main purpose of this second study is to collect information about your body’s immune response; however, we will also collect safety data about aerosol BCG challenge to supplement the information from the TB041 study.
What does the trial involve?
Overall, the study will recruit 65 people into five groups.
Once assigned to a group, volunteers will be randomly allocated either to inhale BCG (Arm A) or to inhale saline (Arm B). Saline is sterile salt water. You will not know which of these arms you are in – we call this blinding.
Group 1 volunteers will then have a follow-up bronchoscopy on Day 2 post challenge. Group 2 will have the bronchoscopy on Day 7 post challenge, Group 3 on Day 14 post challenge, Group 4 at 1-month post challenge and Group 5 at 2-months post challenge.
Your participation in the trial will last for approximately six months, and includes 8 visits to clinic, plus a visit to be screened for eligibility. For full details of the study, click here.
Is there any reimbursement for the trial?
Participants are reimbursed from £685 to £725 for their time and travel. Full details of the reimbursement can be found in the volunteer 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 risks and side effects of the proposed trial procedures are:
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 (described in more detail here) (jumps to full volunteer 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 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.