REpurposing SirolimUS in Compensated Advanced Chronic Liver Disease. The RESUS Proof of Concept Study
Status:
Recruiting
Trial end date:
2024-07-31
Target enrollment:
Participant gender:
Summary
Background: Advanced liver scarring leads to liver failure, liver cancer and premature death.
It mainly affects people in the working age group (18-65 years) and is the only major cause
of death that is still increasing every year in the UK. It costs the NHS £2.1 billion a year.
This will continue to rise due to increasing alcohol misuse and the obesity crisis.
Advanced liver scarring remains incurable as there is no treatment to slow progression of
scarring. Sirolimus is a medication that has been used to prevent rejection after organ
transplantation for over 20 years. It reduces liver scarring, improves liver functioning and
prolongs life in animals. It has also been shown to reduce liver scarring in patients after
liver transplantation. Sirolimus, therefore offers a potential treatment option for liver
scarring.
Question and Objectives: If used in patients with advanced liver scarring, can sirolimus slow
the progression of scarring? The main objective is to undertake a small-scale study (proof of
concept) to investigate if sirolimus could slow the progression of scarring in patients with
advanced liver scarring using clinically relevant biomarkers, which will see if the liver
responds to treatment. How it will be done: The study will be conducted in Nottingham
University Hospitals NHS Trust. 45 patients with advanced liver scarring will be randomly
given either sirolimus or placebo tablets daily for 6 months. Participants will have a liver
biopsy and a MRI scan at the start and end of the study to measure the change in the
biomarkers of liver scarring. A reduction in these markers will indicate successful
treatment. Participants will be monitored for safety of the drug. Potential Impact: If found
efficacious, sirolimus would provide an acceptable treatment for patients with advanced liver
scarring and would also save a substantial sum of money for the NHS.