Objective
Type 1 diabetes is a life-long illness in which beta cells (the cells that make insulin) are damaged and cannot produce insulin. However, when patients are first diagnosed, not all beta cells may have been damaged and some can remain, meaning patients can still produce some insulin. If these beta cells can be protected, complications and symptoms of type 1 diabetes can be reduced. This means that blood sugar levels can be controlled better and serious complications like eye problems and heart attacks may be prevented.
Many studies have been carried out which have tested treatments for protecting beta cells and some have shown promise. However, there is uncertainty around which treatments might be most effective and whether these treatments would be acceptable to patients (in terms of side effects, benefits, how the treatment is taken etc.). The aim of the research is to determine which treatments to protect beta cells are effective and most acceptable to patients with newly diagnosed type 1 diabetes.
Background Rationale
Many clinical trials (over 165) have been carried out which have focused on treatments that might protect beta cells and therefore reduce complications and symptoms for patients with type 1 diabetes. These trials studied many different types of treatments, from keeping good glucose control to immunotherapy-based drugs (drugs that suppress the immune system), vitamins and many others. Although there is lots of evidence available, it is difficult to tell which treatments might be most effective as they have mostly only been compared against placebo or no treatment. Our study would allow the undertaking of statistical methods to get a better understanding of which of the treatments might work best, allowing future research to then focus on a smaller group of effective treatments which could be tested against each other in trials. Also, not much research has been carried out into what patients or parents of patients might think about these potential treatments. To help decide which treatments might be best, we would speak to patients and parents, as well as clinicians, about their opinions on different potential treatments, their side effects, how they are taken, their benefits etc. to help us better understand what patients would want from a treatment.
Description of Project
AIMS
The aim of this research is to determine which of the treatments that protect beta cells are most effective and acceptable to patients with newly diagnosed type 1 diabetes.
BACKGROUND
Type 1 diabetes is a life-long illness in which beta cells (the cells that make insulin) are damaged and cannot produce insulin. However, not all beta cells have been damaged at the time that patients are first diagnosed, meaning they can still produce some insulin. If these beta cells can be protected, blood sugar levels can be controlled better and serious complications like eye problems and heart attacks may be prevented. Many studies have been carried out which have tested treatments for protecting beta cells and some have shown promise. However, there is uncertainty around which treatments might be most effective and whether these treatments would be acceptable to patients (in terms of side effects, benefits, how the treatment is taken etc.).
METHODS
We will do the following:
- update a systematic review (a type of research where all the evidence relevant to a certain research question is found and analysed) that we have previously undertaken with the latest evidence.
- statistical method called a network meta-analysis will be used to compare all the different treatments for protecting beta cells to show which are most effective or if combinations of treatments may be effective.
- an in-depth safety profile of each treatment.
- interviews will be carried out with type 1 diabetes patients (adults and adolescents) as well as parents/guardians of children with type 1 diabetes to discuss how acceptable these treatments are
- interviews with diabetes clinicians will be undertaken to explore their opinions on what they think might work well in patients and what may not.
RELEVANCE OF THIS PROJECT
No one else anywhere is carefully and systematically comparing the different treatments for beta-cell preservation in type 1 diabetes. The importance of this work cannot be over-stated because it has the power to inform the design of future treatment studies in newly diagnosed patients with type 1 diabetes. It allows a transparent review of the many studies that have been undertaken in this area without any potential biases associated with pharmaceutical companies or by researchers. If undertaken well, the results of our study will lead to better diabetes control and fewer complications for people newly diagnosed with type 1 diabetes. Our more ambitious goal is to use the results of this study to achieve long-term delay and prevention of type 1 diabetes in those people who are at risk of developing it.
FUTURE PLANS
Recommendations for the best treatments in newly diagnosed type 1 diabetes patients will be made through publications, research and patient meetings so that these can be made available to patients, or else assessed in large head-to-head clinical trials. This will lead to treatments, or combinations of treatments, to protect beta cells being available for patients who are newly diagnosed with type 1 diabetes, and potentially also those at risk of type 1 diabetes.
INVOLVING PEOPLE WITH DIABETES
This project has been discussed with patients with type 1 diabetes and parents/guardians of younger patients. A group of ten patients/parents have agreed to be the supporting PPI group for this project, along with three patient co-applicants. They have helped develop the application and the plain English summary. They will help determine important outcomes, inform the focus group questions and assist in communicating the results to the wider public.
Anticipated Outcome
If successful, the study has the potential to transform how researchers around the world approach the design of clinical studies to protect beta cell function. The results will be transparent and unbiased and will be based solidly on patient and clinician preferences. It will take into account, not just how well the medicine works but also how safe it is and how effective and practical it is to take.
We feel this aspect of study design has sadly been lacking in our field. We have been inspired by the work done by our colleagues in the multiple sclerosis field who have undertaken a project very similar to this and who will be supporting and steering our project. Our colleagues in the multiple sclerosis field are now undertaking a world leading study to prevent this disease and we can learn a lot from them.
There are many international efforts now to identify children and adults who will develop type one diabetes in the future. Our study will inform how medicines can be tested for them, in a sequential manner so that we can achieve long-term delay of this condition. Our patients tell us this is a very worthwhile project and this is a good time to undertake this piece of work.
Relevance to T1D
This project will help to focus a complex research area on beta cell protection in patients with newly diagnosed type 1 diabetes. The benefits to patients could be significant because protecting beta cells, either with the best treatments individually or in combination, can help to reduce symptom burden and diabetes complications. Most excitingly, the best treatments can be tested in people at risk of developing type 1 diabetes to see if we can delay its onset. Indeed, a treatment called teplizumab has recently been licensed in the USA which delays people getting type 1 diabetes by about 2-3 years. The race is now on to find other treatments that can bring about additional delay. In this way, by identifying and possibly combining the best treatments, we can possibly bring about long-term delay to people getting type 1 diabetes.
We hope that the understanding that comes from this study can be taken forward to clinical trials as soon as the study is finished. Taking the findings of clinical trials to a licensed treatment can take many years but we believe this is a worthwhile journey and one which cannot be travelled without knowing which treatments are most worth testing.