REpurposing SirolimUS in Compensated Advanced Chronic Liver Disease. The RESUS Proof of Concept Study

• Status: Recruiting
• Trial end date: 2024-07-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nottingham University Hospitals NHS Trust
• Treatments: Liver Extracts; Sirolimus

Criteria

Inclusion Criteria:

• capable of giving informed consent

• aged 18-70 years

• compensated advanced chronic liver disease (Child Pugh class A) due to excess alcohol consumption or fatty liver disease

• willing to and able to undergo percutaneous or endoscopic ultrasound-guided liver biopsy at baseline and at 6 months

Exclusion Criteria:

• inability to provide informed consent

• inability to comply with the study protocol

• subjects who may be unavailable for the duration of the treatment course, likely to be noncompliant, or who are felt to be unsuitable by the Investigator for any other reason

• previous history of decompensation of liver disease or liver cancer

• women who are pregnant or breastfeeding

• unable or unwilling to use highly effective contraception during and 12 weeks after the trial participation

• history of allergy or adverse event to sirolimus

• previous or current use of sirolimus

• concurrent use of experimental agents

• an unstable or uncontrolled medical disorder which in the investigator's opinion precludes recruitment within the trial

• major medical comorbidities (e.g., end-stage organ disease, cancer or immunodeficiency)

• increased risk of infectious complications (e.g., immunodeficiency, recent live vaccination)

• surgery within the past 6 months or an anticipated requirement for surgery during the study period