BCG Revaccination Study in Diabetic and Non-Diabetic Adults (TB046)
What is the purpose of this study?
We are a tuberculosis (TB) vaccine research group. We are working on ways to protect people from getting infected with TB. TB is a disease caused by a bacterium (Mycobacterium tuberculosis) and remains one of the top 10 causes of death worldwide. BCG (Bacille Calmette-Guérin) given as an injection is the only vaccine currently licenced for use against TB, but it is not always protective.
There has been recent interest in giving a second dose (“booster”) of BCG by a different route, which might make it work more effectively than an injection. One other way vaccines can be given is by turning them into an aerosol (fine mist) and breathing them in. This study is going to look at whether this way of giving a second dose of the BCG vaccine gives a stronger immune response compared to a conventional injection.
The purpose of this study is to understand more about how the immune response is different when the BCG vaccine is given in a different way.
Why are people with Diabetes needed for this study?
People with Diabetes are at an increased risk of a range of medical conditions, and they are also more likely to develop infections. There is particularly strong evidence that Diabetes increases the risk of developing, and becoming sick from, TB infections. Therefore, improving vaccines which protect against TB is particularly important in this group of people. To achieve this, it is vital to understand how responses to TB vaccines is different in people with diabetes. We will therefore be recruiting both people who have Type 2 Diabetes and those who don’t.
We will compare how the immune system responds to BCG re-vaccination in people with and without diabetes to understand ways that we can improve vaccines for Diabetic people.
FAQ
What is BCG?
BCG is a strain of the bacteria which causes infection in cattle. BCG is a live vaccine, meaning the bacteria in the vaccine are still alive but are weakened so that they do not cause TB disease.
What is an aerosol vaccination?
An aerosol is a fine mist of very small liquid particles. They are produced by a special device called a nebuliser (similar to an inhaler) which takes liquids and squeezes them through a very fine mesh using sound waves. The mist is inhaled into the lungs.
Many medicines for asthma, emphysema, and other respiratory diseases are already given by inhalation. It is not painful to have an aerosol vaccination.
Is the aerosol BCG vaccine safe?
BCG is one of the most widely used vaccines in the world. Several billion people have safely been given the vaccine over the past 100 years, and serious complications are rare. BCG is usually given as an injection under the skin and is not licensed as an aerosol inhalation. It has been given as an aerosol in three previous trials in the 1960s and 70s as well as in our group’s studies (TB041, TB043 and TB044). The TB041 study has now finished with no safety concerns. The TB043 and TB044 studies are ongoing and we are continuing to collect safety data, but there have been no safety concerns to date.
What does the study involve?
The study involves 36 people in 3 different groups (12 volunteers per group). We will recruit 12 volunteers with Type 2 Diabetes and 24 who are not diabetic. Although the number of visits is the same for all the groups, what happens at those visits is different. (See Figure 1)
For full details of all visits, please read the participant information sheet.
Figure 1. Study timeline to show study visits for different groups
What does the study involve for Volunteers without Diabetes?
People who don’t have Diabetes will be enrolled into either group A or B (24 people in total).
Volunteers in these groups will either have BCG revaccination as an injection, or inhaled as an aerosol.
14 days after having their vaccination, volunteers will have washings taken from the lungs in a procedure called a bronchoscopy. This will be performed by an experienced NHS respiratory doctor.
Full details of what this procedure involves can be found in the participant information sheet.
There will also be five short follow up visits only to collect blood samples and check symptoms.
What does the study involve for Volunteers with Type 2 Diabetes?
All volunteers with Type 2 Diabetes will be enrolled into group C (12 people). Volunteers in this group
will all have BCG revaccination as an injection.
They will have the same number of study visits as the other groups, but they will not have a bronchoscopy. In the 6 follow up visits blood samples will be collected and symptoms checked.
Is there any reimbursement for the study?
Participants are reimbursed up to £1095 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.
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 study?
The main risks and side effects of the proposed study procedures are listed here.
- Blood samples: drawing blood may cause slight pain and occasionally bruising
- BCG injection: The most common side effects are swelling and redness, a small ulcer can form some weeks later at the site of vaccine injection. This usually heals over a few months and leaves a small flat scar. It is also possible to develop some mild swelling of glands in the armpit. These are natural reactions to the vaccine. Rare side effects include inflammation of glands, sometimes with leakage of fluid from the swellings.
- Aerosol inhalation of BCG: Inhalation is a safe route for giving medicines. To date over 100 volunteers have received inhaled BCG across our TB041, TB043 and TB044 studies, with side effects only lasting a 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 generally occur within the first few days of BCG vaccination. A doctor will be available throughout the vaccination and the clinic room is equipped with
- oxygen and medications to treat any other symptoms.
- Bronchoscopy: (Participants without Diabetes Only) 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 by an experienced NHS respiratory doctor, 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 for any reaction following both the vaccination and, if applicable, the bronchoscopy.
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 perform any more research procedures, although occasionally we might 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 study, see the participant information sheet.
If you have any other questions about participating then don’t hesitate to contact the study team by email at vaccinetrials@ndm.ox.ac.uk