Dr Palak Trivedi

Aim

We aim to explore the potential of a new treatment to slow the progression of PSC and improve the quality of life for patients.

Background

Primary sclerosing cholangitis (PSC) is a rare liver disease where the body attacks itself, causing inflammation and scarring of the bile ducts and liver. This causes bile to stop flowing properly, leading to repeated infections, liver failure and, in some cases, cancer. In 80% of people with PSC the body will also attack the bowel, which can lead to inflammatory bowel disease (IBD).

The combination of the two conditions results in a 15-30% lifetime risk of bowel cancer, and patients require a colonoscopy every year to look for this complication.

PSC affects approximately 3,600 people in the UK. The condition can develop at any age, but has a particular impact in people under 40 years.

At present, the treatment of PSC is focused on managing the symptoms, not treating the cause. Unfortunately, there is no cure, nor any medication that has been shown to improve survival. Liver transplantation is the only lifesaving treatment. Although a very rare disease, PSC accounts for 10-15% of all liver transplants performed in the UK and is now the leading reason for transplantation in several European countries.

Transplantation is risky and costs around £1m per patient (including aftercare). Moreover, PSC returns in around 30% of people who have had a liver transplant.

The team, led by researchers at the University of Birmingham, has one of the largest PSC research programmes globally, with a dedicated PSC-IBD clinic as part of the Centre for Rare Diseases. The research team is partnering with PSC Support, the leading patient organisation for people living with primary sclerosing cholangitis, which has a wealth of experience working with medicines' regulators on drug development for this condition.

Through this partnership the team aims to explore the potential of a new treatment to slow the progression of PSC and improve the quality of life for patients.

It has been shown that the makeup of gut microorganisms in PSC are different to that found in people without liver and bowel inflammation, and that this is one of the drivers of disease development. The Birmingham research team will by trialling a treatment, called ‘faecal microbiota transplantation’ (FMT), which involves taking stool from the gut of healthy donors, treating it in a laboratory and transferring it to the bowel of people with PSC to restore their abnormal gut bacteria balance.

Early research has shown that FMT is safe, is effective in treating IBD and improves liver blood test results in some individuals. The grant from LifeArc and PSC Support enables the team to accelerate and scale up their research to answer the key questions that will allow them to take this treatment from idea to direct patient benefit.

How will we do it?

This study will test the safety and long-term effects of FMT as a treatment for people with PSC. It will also improve understanding around which specific micro-organisms in donor stool are most important, and how this information can be used to enhance the product for large scale rollout.

Researchers will randomly allocate individuals with PSC to receive either FMT once a week for 8 weeks (group 1), or placebo (an inactive FMT equivalent; group 2). Each group will continue to receive routine standard of care for symptoms and treatment for their IBD. Both groups will be observed for another 40 weeks, meaning the trial will run for 48 weeks. The team will then measure how successful the treatment has been in improving liver blood test results, the burden of scarring in the liver, activity of IBD and quality of life.

What will we do next if we get a positive result?

It is hoped that this study will lay the foundation for future work on a larger scale, with a view to making FMT available globally. In parallel, PSC Support will work with the wider study team to support delivery of FMT as a treatment after the trial has finished. This will include submitting trial documents for the UK medicines’ regulatory agency to broaden access to new treatments for people living with the disease.