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

Why is JDRF funding this project?

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 type 1.

Why combine multiple immune-targeting drugs?

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 seven drugs 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.

What are the hurdles with testing combinations of drugs?

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 at the same time rather than one after another.

What are the aims of Colin’s research project?

Colin wants to develop a platform where trials of multiple immune therapies can be conducted easily and quickly at a fraction of the cost. His vision is for the platform to effectively serve as a large network of trials so that only one control group (a group of study participants who are given a non-active placebo drug) is needed across trials of all the different drugs. So, each of the seven immune drugs being looked at and all their combinations would only need to be trialed once for their effects to be directly compared to all others.

What will Colin do in this research project?

First step: trialing verapamil with teplizumab together

The first part of Colin’s project is to test whether using multiple immune therapies protects beta cells more effectively than when they are given alone. He is doing this in the form of a clinical trial giving people recently diagnosed with type 1 two immune-targeting drugs: verapamil and teplizumab. The most important thing Colin will be monitoring is the safety of giving people the two drugs together. This trial will not only demonstrate whether this combination safely preserves beta cell function better than a single immune therapy but could also provide clues as to whether other drug combinations would work.

Next step: Developing a trial design for testing multiple drugs

Colin will then use his experience of testing verapamil and teplizumab together to establish a wider trial design for rapid testing of different combinations of beta cell preserving therapies. This design will include elements of the ‘adaptive trial design’ being used in other research fields and form the basis of the T1D Plus platform. One aspect of his design will be introducing a ‘fail fast’ assessment to stop early any drugs trials that are not showing potential to benefit people with type 1, saving researchers and participants crucial time, effort and funds. For safety reasons, the trial platform 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 with type 1?

Combinations of immune therapies could improve our ability to slow the autoimmune process that destroys beta cells in type 1 diabetes. Slowing the development of type 1 has the potential to reduce the variation people with type 1 experience in their blood glucose levels and reduce the frequency and risk of hypoglycaemia. In turn, this will reduce the risk of long-term complications that come with diabetes. As well as these biological advantages, immune therapies can limit the effort and stress associated with the daily challenges of living with type 1 diabetes.

Is JDRF 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 get involved in research, browse their list of type 1 diabetes clinical trials that are recruiting participants.