Faecal Microbiota Transplantation for Liver Cirrhosis (CHiFT)

Faecal Microbiota Transplantation to Prevent Complications, Progression and Mortality of Liver Cirrhosis

The purpose is to investigate the effect of fecal microbiota transplantation (FMT)on complications, progression, and mortality of cirrhosis. Further, the investigators want to examine the impact of FMT on gut barrier function, systemic inflammation, and immune responses.

Study Overview

• Status: Recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Biological: Placebo; Biological: Faecal microbiota transplantation

Detailed Description

Patients with liver disease have a disturbed gut microbiota. This is often associated with disease progression and development of complications, so called episodes of decompensation. In this study we will change the microbiota of these patients by transferring a healthy microbiota through faeces from a healthy donor, a procedure known as a faecal microbiota transplantation (FMT). In this this study we will examine the effect of FMT on the prognosis and disease progression of the patients. Further, we will examine the mechanistic effects of FMT in these patients. We will at random divide 220 patients admitted with decompensation of liver cirrhosis evenly into two groups. One group will receive FMT and the other group will receive placebo. After the treatment, we will follow the patients for one year and examine disease progression as well as changes in their gut microbiota, gut barrier, and immune function.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Karen Louise Thomsen, PhD; Phone Number: +4526949260; Email: karethom@rm.dk
• Study Contact Backup: Name: Lotte Lindgreen Eriksen; Phone Number: +4529279784; Email: lotter@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Department of Hepatology and Gastroenterology, Aarhus University Hospital
    • Contact: Karen Louise Thomsen, PhD; Phone Number: +4526949260; Email: karethom@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-75 years
• Liver cirrhosis with Child-Pugh score 7-12
• Hospital admission due to acute decompensation (ascites, gastrointestinal bleeding, bacterial infections, hepatic encephalopathy, alcoholic hepatitis)
• Maximum of 1 organ failure defined by CLIF-SOFA score

Exclusion Criteria:

• Untreated malignancy apart from hepatocellular carcinoma within the Milan criteria or non-melanoma skin cancer
• Untreated viral hepatitis
• HIV
• Inflammatory bowel disease
• Celiac disease
• Pregnancy
• Unable to participate based on medical judgement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Faecal microbiota transplantation; The patients will receive three applications of FMT consisting of 50 g cryopreserved, homogenized faeces from healthy donors. The faecal material will be dispensed into double-coated, acid-resistant enterocapsules or cryobags. Faeces will be screened according to international guidelines.	Biological: Faecal microbiota transplantation; All participant will receive three applications of either FMT or placebo and afterwards followed for 1 year.; Other Names: FMT
Placebo Comparator: Placebo; The placebo products is produced from a suspension of glycerol, saline and food colouring and cannot be distinguished from the active FMT products.	Biological: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death or re-admission due to episode of acute decompensation in FMT treated versus placebo treated patients.	Using data from the patient journals, we will be able to examine the exact time to event in each of the patients. To compare the to groups, hazard ratios will be calculated.	1 year
Frequency of patients who have died or experienced a new episode of decompensation at 3 months of follow-up in FMT treated versus placebo treated patients.	At three months follow-up of the first 40 patients, we will conduct an interim analyses. The primary outcome measure is frequency of patients, who have died or developed a new episode of decompensation. We will draw the data from electronic patient charts and from follow-up visits. The frequency will be compared using Chi2 test.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gut microbiota beta-diversity (Bray-Curtis index, taxonomic abundance) during one year in FMT treated versus placebo treated patients by 16S sequencing.	In stool and saliva samples collected before and at 5 time points following the intervention, we will measure the gut microbiota composition.	1 year
Change in plasma concentration of gut translocation markers; lipopolysaccharide binding protein, soluble CD14, fatty acid binding protein 1 during one year in FMT treated versus placebo treated patients by ELISA.	In blood samples collected at baseline and at follow-up visits, we will measure these plasma proteins by ELISA.	1 year
Change in plasma concentration of pro- and antiinflammatory cytokines; IL-6, IL-1beta, TNF-alpha, IL-8, IL-10 in response to the intervention by luminex.	In blood samples collected at baseline and at follow-up visits, we will measure these plasma proteins by luminex.	1 year

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Hvidovre University Hospital; Aalborg University Hospital; Aalborg University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Anticipated): May 31, 2026
• Study Completion (Anticipated): May 31, 2027

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: June 18, 2021
• First Posted (Actual): June 21, 2021

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: November 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Ascites; Gastrointestinal bleeding; Hepatic encephalopathy; Hepatorenal syndrome; Alcoholic hepatitis; Spontaneous bacterial peritonitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 1-10-72-302-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No