Tuberculosis Vaccine Trial (TB043)
Tuberculosis Vaccine Trial (TB043)
What is the purpose of this trial?
Tuberculosis (also known as TB) is a disease caused by a bacterium (Mycobacterium tuberculosis) that remains one of the leading infectious disease killers worldwide. BCG is the only vaccine currently licenced for use against TB. BCG has some effect against TB disease in childhood, but it is not good enough at protecting against disease in adulthood, which leads to the majority of TB deaths. We are working on developing better vaccines against TB in the hope of providing greater protection than that given by the BCG alone.
It is not easy to work out which vaccines work well and which do not. To help us, we are studying how people’s immune systems respond to BCG. BCG itself is a type of bacteria, similar to TB but much weaker so it does not cause disease in people with normal immune systems. For the purpose of this study, we are using BCG to mimic an infectious response. This is called a BCG “challenge”. We are giving BCG either as an inhaled aerosol (as this is the natural route via which TB infects people) or as an injection. We then study the effects on the lungs and in the blood. This study does not use virulent (infectious) TB bacteria at all and there is no risk of getting TB. We hope that this study will help improve our understanding of TB infection for future TB vaccine development.
Am I eligible to participate?
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 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 81 people into seven groups.
Once assigned to a group, 65 volunteers will be randomly allocated either to inhale BCG (10 volunteers per group) or to inhale saline (3 volunteers per group). Saline is sterile salt water. You will not know which of these arms you are in – we call this blinding. 6 volunteers will receive BCG via the standard injection route, together with inhaled saline. In group seven, 10 volunteers will receive aerosol BCG without randomisation or blinding.
All volunteers will then undergo a bronchoscopy (a camera test looking at the lungs). Group 1 volunteers will have a bronchoscopy on Day 2 post challenge. Group 2 will have the bronchoscopy on Day 7 post challenge, Group 3,Group 6 (the injection group), and group 7 on Day 14 post challenge, Group 4 at 1-month post challenge and Group 5 at 2-months post challenge.
For most volunteers, 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. During the COVID-19 pandemic there will be two-three additional short visits for COVID-19 tests, prior to receiving the BCG and prior to the bronchoscopy. For some volunteers in groups 3-5 or 7 there will all be an additional COVID-19 test prior to induced sputum.
Volunteers in group 7 will be asked to wear a specially adapted collection face mask at some visits to see if this can detect breathed out BCG.
Volunteers in group 6 and up to 10 volunteers in group 3 and/ or 7 will be asked if they are willing to attend for an optional visit at 12 months to look at prolonged immune responses.
For full details of the study, including the changes we have made due to COVID-19, please click here.
Is there any reimbursement for the trial?
Participants are reimbursed from £705-£750 for their time and travel. An additional £45 will be reimbursed if the optional 12-month visit is undertaken. 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:
- Blood samples: drawing blood may cause slight pain and occasionally bruising
- Aerosol inhalation of BCG: Inhalation is a safe route for giving medicines. In our TB041 study, there were no serious side effects. All side effects seen were of been of short duration. 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 challenge and the clinic room is equipped with oxygen and medications to treat any other symptoms.
- Intradermal injection of BCG: Common side effects include superficial discomfort and redness at the injection site. A small ulcer usually forms about a week later at the site of the injection. This usually heals over a few weeks to months and leaves a small flat scar. It is also possible to develop some swelling of glands in the armpit, but usually less than one centimetre across. More uncommonly, some people experience swelling of the glands in the armpit or an ulcer that leaks fluid at the injection site (less than 1 in 100) or more rarely severe inflammation of glands leading to abscesses (less than 1 in 1000) or an allergic reaction to the vaccine.
Some of these side effects mimic COVID-19 infection. We have set out clear guidelines about how we will deal with this in the study. Further information can be found here. A trained member of the study team will discuss this information with you at your screening visit.
A trained member of the study team will discuss this information with you at your screening visit.
- 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).
- Induced sputum (volunteers who have received BCG only): This is a simple and safe non-invasive procedure. Salty saline is inhaled to help you cough up a phlegm (sputum) sample. For some people this may lead to coughing spasms. You will be asked to stay in clinic until any coughing stops. Very rarely the salty saline can cause your airways to spasm. This is extremely unlikely in people with no history of asthma, and is quickly reversible with medication. A member of the clinic team would be with you throughout the sample process.
You will be monitored in clinic following aerosol BCG inhalation or BCG injection 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.