PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial

Abstract

IntroductionPatients with advanced cirrhosis have enteric bacterial dysbiosis and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxaemia, inducing innate immune dysfunction which predisposes to infection, and development of complications such as bleeding, sepsis and hepatic encephalopathy. This feasibility study aims to assess the safety of administering faecal microbiota transplantion to patients with cirrhosis and explore the effect of the intervention on their prognosis by achieving restoration of a healthy gut microbiome.Methods and analysisA PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation is a single-centre, randomised, single-blinded, placebo-controlled study evaluating faecal microbiota transplantation (FMT) against placebo. Patients with advanced but stable cirrhosis with a Model for End-Stage Liver Disease score between 10 and 16 will be recruited. Twenty-four patients will be randomised to FMT plus standard of care (as per our institutional practice) and eight patients to placebo in a ratio of 3:1. Patients will be evaluated at baseline before the study intervention is administered and at 7, 30 and 90 days post-intervention to assess safety and adverse events. FMT/placebo will be administered into the jejunum within 7 days of baseline. The primary outcome measure will be safety and feasibility as assessed by recruitment rates, tolerability and safety of FMT treatment. Results will be disseminated via peer-reviewed journals and international conferences. The recruitment of the first patient occurred on 23 May 2018.Ethics and disseminationResearch Ethics approval was given by the London South East Research Ethics committee (ref 17/LO/2081).Trial registration numberNCT02862249 and EudraCT 2017-003629-13.

Modulating the gut–liver axis and the pivotal role of the faecal microbiome in cirrhosis

“…38 Our group has recently completed a safety and feasibility study of FMT in advanced but stable cirrhosis (MELD score 10-16). 39 This study showed that FMT was safe and feasible in this patient group, with a reduction in plasma ammonia levels in FMT treated patients persisting for up to 30 days after treatment. Ammonia is a microbial metabolite and has a central role in the pathogenesis of HE, suggesting a potential role for the use of FMT in the management of this debilitating condition.…”

Role of Microbiota in Pathogenesis and Management of Viral Hepatitis

“…Woodhouse et al have observed in a PROFIT clinical trial the benefits of fecal microbiota transplantation in the small bowel of cirrhotic patients (Woodhouse et al, 2019 ). Meiglani et al ( 2020 ) also observed that cirrhotic patients with antibiotic-resistant Clostridioides difficile infection (CDI) responded well after FMT treatment.…”

Intestinal permeability and bacterial translocation in patients with liver disease, focusing on alcoholic aetiology: methods of assessment and therapeutic intervention

“…The trial is aiming to assess not only the safety and tolerability of administering FMT to patients with cirrhosis, but also to try and quantify the effects through measuring changes to the recipient stool microbiome, plasma endotoxin and bacterial DNA levels as well as inflammatory cytokines. 128 …”