T1D Plus: A clinical trials platform testing multiple drugs to treat type 1 diabetes

Thanks to funding from Breakthrough T1D UK, Professor Colin Dayan at Cardiff University is setting up a clinical trials platform called T1D Plus. At least 10 different treatments have already been shown in clinical trials to slow the immune system attack on the insulin-making beta cells in the pancreas that causes type 1 diabetes (T1D), enabling people to keep making their own insulin for longer. Known as disease modifying therapies, T1D Plus will allow several of these drugs to be tested at once and in combination with each other. This will tell us what the most effective therapies are, while saving time and money compared to traditional trial designs, and accelerating us towards new treatments for T1D.

Preserving insulin-making beta cells

Because the immune system goes awry in type 1 diabetes, treatments that target the immune system have huge potential to prevent, treat and even cure type 1. By the time someone is diagnosed with type 1, their immune system has destroyed around 80% of their insulin-producing beta cells. Incredibly, preserving 30-40% of our beta cells is probably enough to prevent someone needing insulin treatment at all. Even keeping just 5% of beta cell function makes managing glucose levels and avoiding hypos easier. This is similar to the honeymoon period that some people experience in the first months after their diagnosis of T1D.

Combining immune therapies

Drugs that target the immune system (known as immune therapies) can have unwanted side effects for the person taking them. So, immune therapies are given at as low a dose as possible to avoid this. None of the disease modifying therapies that can slow the autoimmune attack in type 1 can be given at a high enough dose to stop the attack completely. So, Colin thinks that giving people with type 1 low doses of multiple different immune therapies could be a way to make them more effective while still avoiding negative side effects.

A new approach to clinical trials

Using standard methods, clinical trials of combinations of treatments are more complex and require more trial participants, time and resources than studies of a single treatment alone. In cancer and other diseases, researchers have overcome this problem by developing a new approach to clinical trials, known as ‘adaptive platform trials’.

In these trials, many drugs or treatment combinations are tested and compared at the same time and rather than one after another and the parts of the trial can be adapted as it progresses. For example, if a drug combination is proving unsuccessful, this part of the clinical trial can be stopped, and participants moved onto different drugs in the trial. New drugs and combinations can be added to the clinical trial too. This flexibility allows Colin to make changes according to new information that comes to light, focusing efforts on the therapies that are most effective for people living with T1D.

Verapamil as a control group

Usually in clinical trials there is a control group of people who receive a non-active placebo, which the results from the group who received the active drug are compared to. In T1D Plus, the control group will be people who are given verapamil, and these will be compared to people who receive verapamil and another disease modifying therapy. Verapamil is an existing drug that improves blood flow to the heart and is used in the UK to treat heart conditions including high blood pressure and angina (chest pain). Taken as a daily tablet, verapamil was also found to slow the progression of T1D in a clinical trial funded by Breakthrough T1D. This means everyone who takes part in the clinical trial will receive a drug shown to delay progression of T1D and preserve the ability to make insulin.

Testing multiple disease modifying therapies

As well as everyone in the clinical trial taking a daily pill of verapamil, different groups of participants will receive a different additional disease modifying therapy. One group will be given an injection of golimumab, an immunotherapy that is used to treat the autoimmune conditions rheumatoid arthritis and ulcerative colitis. Another group will receive an infusion of antithymocyte globulin (ATG), an immunosuppressant drug used in organ transplants, over two days. Once these groups are up and running, Colin will add another group who will receive a daily tablet of baricitinib, a drug given to people with rheumatoid arthritis and alopecia that one of our clinical trials found can preserve insulin production in people with T1D.

Who can take part in the T1D Plus clinical trial?

The clinical trial will take place at study sites across the UK, Europe and Australia. Colin will recruit people who have been diagnosed with T1D for less than three months, and we will update this page when the clinical trial opens. For safety reasons, T1D Plus is currently only being run in adults, but if it proves successful, the design will be extended in the future to younger participants.

How will this research help people living with T1D?

Combinations of disease modifying therapies could improve our ability to slow the autoimmune process that destroys beta cells in T1D. Slowing the development of T1D has the potential to reduce the variation people with T1D experience in their blood glucose levels and reduce the frequency and risk of hypos. In turn, this will reduce the risk of long-term complications that come with diabetes. As well as these biological advantages, these therapies can limit the effort and stress associated with the daily challenges of living with T1D.

Is Breakthrough T1D UK funding any other research like this?

We funded Colin to set up and run the UK T1D Research Consortium, which has created a network of 24 research sites across the UK, all running clinical trials for type 1 diabetes. If you’d like to take part in research, browse their list of type 1 diabetes clinical trials that are recruiting participants.