Professor Debbie Shawcross, Professor of Hepatology and Chronic Liver Failure at the Institute of Liver Studies at King’s College London and her team are soon to start work on a trial looking to assess the effectiveness of FMT to improve outcomes in patients with cirrhosis through the PROMISE trial.
There is an evolving crisis of chronic liver disease (CLD) in the UK and it is the only major chronic disease which is on the rise. The advanced stages of CLD, known as cirrhosis (a hardening and scarring of the liver), is the third biggest cause of death and loss of working life years behind heart disease and self-harm. People die from cirrhosis young with more than 1 in 10 in their 40s. Patients with cirrhosis are very susceptible to infections, antibiotics become ineffective and patients may become infected with 'super bugs'. There is an urgent need for antibiotic-free approaches.
There are increased numbers of 'unfriendly' bowel bacteria in patients with cirrhosis which emit substances which are harmful to health and disrupt the immune system. The PROMISE trial is looking to establish whether it could be beneficial to replace the unfriendly bowel bacteria in patients with cirrhosis with bacteria donated from a healthy person by performing a type of bowel bacteria transplant (known as faecal microbiota transplantation or FMT).
The team have recently performed a preliminary trial of FMT which was placed into the bowel with the help of a flexible camera (endoscopy). The study showed FMT was safe with no serious side effects, but patients told the team that they would prefer to take tablets rather than have an endoscopy. The team have therefore developed tasteless and odourless capsules which contains dried stool from a healthy donor.
Patient participants in the PROMISE trial will be selected at random to have FMT treatment or placebo, and both the study team and the patients will not know which treatment they are taking. The patients will need to take 5 capsules every 3-months. Patients will continue treatment for a total of 21-months or until they develop their first infection leading to hospital admission and will be followed-up for a maximum of 2-years. The study will also examine if having FMT will reduce the side effects of cirrhosis, and if it has beneficial effects on the liver and immune system. The study team will look at whether it reduces hospital admissions, the incidence of 'super-bug' infections and death. Laboratory studies led by Dr Lindsey Edwards, a mucosal immunologist specialising in bacterial infections and antibiotic resistance within Prof Shawcross’ team will look at whether FMT treatment will help the immune system fight infection; thus reducing the need for antibiotic prescription. As patients with chronic liver disease are particularly at risk of developing life-threatening infections and acquiring antibiotic resistance.