Trial of Faecal Microbiota Transplantation in Cirrhosis

NCT02862249 | Completed Phase 3 DMC

• 1 other identifier: PROFIT-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with advanced cirrhosis have enteric dysbiosis with small bowel bacterial overgrowth and translocation of bacteria and their products across the gut epithelial barrier. This culminates in systemic inflammation and endotoxemia which induces innate immune dysfunction predisposing to infection and development of complications such as bleeding, sepsis and hepatic encephalopathy. It also plays a key role in the natural history of cirrhosis by influencing the rate of progression to advanced liver disease and terminal liver failure. The investigators propose an intervention utilising Faecal Microbiota Transplantation (FMT) from a healthy donor to modify the gut microbiome alleviating gut dysbiosis and immune dysfunction. This may ultimately reduce the progression to chronic liver failure and the development of infection and organ dysfunction. The primary objective of this study will be to assess whether stabilising gut dysbiosis with FMT in patients with advanced cirrhosis is both feasible and safe.

Conditions

Cirrhosis of the Liver

Outcome Measures

Primary Outcomes (2)

• Assessment of the feasibility of FMT

  Assess recruitment rates and tolerability of FMT (e.g reflux rates): * \>50% fulfil inclusion/exclusion criteria (of all screened- about 160) * \>25% consent rate (of all those fulfilling inclusion/exclusion criteria about 80 patients) * \>80% randomised patients treated successfully and completing study up to D90 (out of those randomised approx 22 patients) * Availability of obtaining sufficient donor samples for the study * Reflux rates of transplanted material \<20% e.g. foul taste, foul smell, nausea, vomiting, indigestion. * Intolerable (resulting in withdrawal from the study GI side effects including diarrhoea, constipation, abdominal pain, flatulence and bloating) of \<20%

  18 months

• Assessment of the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  1. Incidence of any transmissible bacterial or viral infection that is deemed to have been acquired from the donor including Clostridium Difficile infection 2. The development of any SAE/SAR or USAR that is not pre-specified or is a known consequence of disease progression or complication of cirrhosis as outlined in section 7.2.5.1 that: results in death/is life threatening/requires hospitalisation or prolongation of existing hospitalisation/results in persistent or significant disability or incapacity.

  18 months

Secondary Outcomes (2)

• To provide preliminary evidence of efficacy for a larger randomised trial

  18 months

• To estimate the costs and resources required to implement this novel therapy in a NHS environment.

  18 months

Study Arms (2)

Faecal microbiota transplantation

EXPERIMENTAL

Faecal microbiota transplantation.

Biological: Faecal microbiota transplantation

Placebo

PLACEBO COMPARATOR

Placebo solution.

Biological: Placebo

Interventions

Faecal microbiota transplantation BIOLOGICAL

The FMT (200mls) will be administered following preparation of the bowel with MoviPrep®, into the duodenum via a gastroscope derived from 50g of fresh donated stool from a healthy donor. The gastroscopy will be performed as per the King's College Hospital Gastroenterology Protocol.

Faecal microbiota transplantation

Placebo BIOLOGICAL

An identical appearing placebo solution (200mls 0.9% normal saline and 12.5% glycerol) will be administered into the duodenum via a gastroscope in a single blinded fashion following preparation of the bowel with MoviPrep®.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years
• Confirmed advanced cirrhosis of any aetiology with a MELD score between 10 and 16. The diagnosis of liver cirrhosis will be based on clinical, radiological, or histological criteria.
• Patients with alcohol-related liver disease must have been abstinent from alcohol for a minimum of 6 weeks.
• Patients must be deemed to have capacity to consent to study.

You may not qualify if:

• Severe or life-threatening food allergy
• Pregnancy or breastfeeding
• Patients treated for active variceal bleeding, infection, bacterial peritonitis, overt hepatic encephalopathy or acute-on-chronic liver failure within the past 14 days.
• Patients who have received antibiotics in the past 14 days.
• Active alcohol consumption of \>20 grams/day.
• Has had a previous liver transplant
• Hepatocellular carcinoma outside of the Milan Criteria (2)
• A history of prior gastrointestinal resection such as gastric bypass
• Patient is not expected to survive the duration of the study (90 days).
• Severe renal impairment (creatinine \>150 µmol/L)
• Inflammatory bowel disease (IBD)
• Coeliac disease
• HIV positive
• Immunosuppression e.g. more than two weeks treatment with corticosteroids within 8 weeks of intervention, active treatment with tacrolimus, mycophenylate, azathioprine

Sponsors & Collaborators

• King's College London: lead
• King's College Hospital NHS Trust: collaborator

Study Sites (1)

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• Woodhouse CA, Patel VC, Goldenberg S, Sanchez-Fueyo A, China L, O'Brien A, Flach C, Douiri A, Shawcross D. PROFIT, a PROspective, randomised placebo controlled feasibility trial of Faecal mIcrobiota Transplantation in cirrhosis: study protocol for a single-blinded trial. BMJ Open. 2019 Feb 15;9(2):e023518. doi: 10.1136/bmjopen-2018-023518.

  PMID: 30772848 DERIVED

MeSH Terms

Conditions

Fibrosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Debbie Shawcross

  King's College London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: August 11, 2016
• Study Start: March 27, 2018
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)