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Trial of Faecal Microbiota Transplantation in Cirrhosis (PROFIT)

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ClinicalTrials.gov Identifier: NCT02862249
Recruitment Status : Recruiting
First Posted : August 11, 2016
Last Update Posted : August 13, 2019
Sponsor:
Collaborator:
King's College Hospital NHS Trust
Information provided by (Responsible Party):
King's College London

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.


Condition or disease Intervention/treatment Phase
Cirrhosis of the Liver Biological: Faecal microbiota transplantation Biological: Placebo Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Other
Official Title: A Prospective, Randomised Placebo Controlled Feasibility Trial of Faecal Microbiota Transplantation in Cirrhosis
Actual Study Start Date : March 27, 2018
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Faecal microbiota transplantation
Faecal microbiota transplantation.
Biological: Faecal microbiota transplantation
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.

Placebo Comparator: Placebo
Placebo solution.
Biological: Placebo
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®.




Primary Outcome Measures :
  1. Assessment of the feasibility of FMT [ Time Frame: 18 months ]

    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%

  2. Assessment of the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 18 months ]
    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.


Secondary Outcome Measures :
  1. To provide preliminary evidence of efficacy for a larger randomised trial [ Time Frame: 18 months ]
    (i) Choosing the optimal primary outcome, and (ii) Estimating the parameters for sample size calculation.

  2. To estimate the costs and resources required to implement this novel therapy in a NHS environment. [ Time Frame: 18 months ]
    Cost effectiveness



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 18-75 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.

Exclusion criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02862249


Contacts
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Contact: Debbie Shawcross +442032993713 debbie.shawcross@kcl.ac.uk
Contact: Charlotte Woodhouse charlottewoodhouse@nhs.net

Locations
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United Kingdom
King's College Hospital NHS Foundation Trust Recruiting
London, United Kingdom, SE5 9RS
Contact: Charlotte Woodhouse       charlottewoodhouse@nhs.net   
Sponsors and Collaborators
King's College London
King's College Hospital NHS Trust
Investigators
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Study Chair: Debbie Shawcross King's College London

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT02862249     History of Changes
Other Study ID Numbers: PROFIT-01
First Posted: August 11, 2016    Key Record Dates
Last Update Posted: August 13, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All information, data and results obtained from study are confidential. Agreement from the Sponsor will be required prior to the public disclosure of any study-related data. It is expected that results from the study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses. All publications and presentations relating to the study must be authorised by the CI.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases