Regulating the immune attack on insulin producing cells
Title of research
Mechanisms of action of peptide immunotherapy for Type 1 diabetes: characterising T cells induced or modified by proinsulin C19-A3
Institutions
Kings College London and Cardiff University
Name of lead investigators
Prof Mark Peakman, Professor of Clinical Immunology
Prof Colin Dayan, Professor of Clinical Diabetes and Metabolism
Research funded by
Diabetes UK and the Diabetes Vaccine Development Centre (New South Wales, Australia)
Who to contact
Ms Rachel Stenson, Senior Trial Manager
Tel: 0781 6240 299
Email: diabetesresearch@cardiff.ac.uk
Recruiting until
February 2014
Total number of participants needed
24
Who can take part?
Inclusion criteria
Participants must be aged between 18 and 40 and have been diagnosed with Type 1 diabetes within the last 100 days.
What is the research about?
In Type 1 diabetes the immune system mistakenly targets insulin-producing beta cells in the pancreas and destroys them as if they were infected. An increasingly promising strategy to prevent the ‘autoimmune’ attack on beta cells is to use a “vaccine”. Like other vaccines, this is injected under the skin to trigger a protective immune response.
Researchers at King’s College London are currently conducting a trial on a vaccine for Type 1 diabetes. The researchers have already demonstrated that the vaccine is safe in people with long-standing Type 1 diabetes. Now they are conducting another study in people recently-diagnosed with Type 1 diabetes, focusing on effectiveness as well as safety. Before and after treatment with the vaccine, changes in participants’ immune responses and in the appearance of their immune cells will be examined by the researchers.
How will it benefit people with diabetes?
Ultimately, if it works, the vaccine could help to preserve insulin producing cells, limiting the severity of Type 1 diabetes in people who already have the condition and preventing it altogether in those who are at risk. This would mean that people with Type 1 diabetes would require much less insulin to control their blood glucose or could even become independent of insulin. This would make blood glucose control much easier, improve their quality of life and reduce or eliminate their risk of complications. Testing and evaluation of the vaccine could be completed within 5-10 years.
What will taking part involve for participants?
Participants will be provide a small sample of blood (about 15ml or three teaspoons) to determine their tissue type and to look for markers of the immune attack that causes Type 1 diabetes. Only about half of people with Type 1 diabetes have the right tissue type to respond to the vaccine being tested and only they can be included in the study. If this vaccine is a success, the researchers will develop a different version for people with other tissue types.
Once the test results are in (after about two weeks) participants with the markers and the correct tissue type will be asked to visit a local research centre in London, Bristol, Cardiff or Newcastle for a morning visit of 3 hours. This will consist of a general examination and further blood tests, including a test of the amount of insulin still being made by the body after a meal.
The blood samples will be analysed within two weeks and if they reveal the presence of an insulin response after a meal (as occurs in 80-90% of people with Type 1 within a year of diagnosis) the participant will be contacted by the research team to arrange the first injection treatment.
The treatments will involve a tiny, almost painless injection under the skin of the arm given in a very similar way to vaccination injections. Everyone in the trial will receive injections once every two weeks for 24 weeks (a total of 12 injections) followed by check-ups for another 24 weeks.
People in the trial will be randomly assigned by computer to one of three groups and neither the participants nor the researcher will know which. Group A will receive only salt water ‘placebo’ injections. Group B will receive peptide injections once every four weeks with placebo injections in between. Group C will receive peptide injections every two weeks. This approach is referred to as a double blind randomised controlled trial and is the ‘gold-standard’ method of evaluating a new treatment.
During the treatment, participants will be asked to provide blood samples to allow researchers to test the response of their body’s immune system and pick up any side effects. Blood tests will also be taken during the trial to see how much insulin the body is making. Participants will also be asked to provide urine samples. Participants will not be told the results of the tests until the end of the trial unless any of the results are not normal and require treatment. At each visit participants will be seen by a nurse or a doctor with training in diabetes care to discuss their insulin treatment and ensure it is helping to keep blood glucose levels within a good range.
What are the risks involved in participating?
Participants may experience bruising or discomfort at the site of the blood tests, as with any blood test. The amounts of blood taken are small enough that they should not cause anaemia or make participants feel fatigued. Participants may experience local red reactions at the site of the injections and it is possible that they might have a severe reaction to the injection which will require treatment. However, the researchers have not seen any severe reactions in the 37 people who have received the injections so far.
All injections will be given with trained staff and equipment on hand in case participants have any problems. If participants do have a severe reaction, no further injections will be given. It is possible that the peptide might weaken insulin production in the pancreases of those who receive it. However, this has not been seen in previous studies and the researchers will be monitoring insulin production every 12 weeks.
Financial remuneration
The research team will reimburse participants for travel expenses incurred while taking part in the trials.
Further information
Additional details regarding the study can be obtained from the Cardiff University website.