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 faecal microbiota transplantation (FMT) on complications, progression, and mortality of patients with liver cirrhosis. Further, the investigators want to examine the impact of FMT on the gut microbiota, gut barrier function, systemic inflammation, and immune function.

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 trial, we will change the microbiota of these patients by transferring a healthy microbiota through faeces from a healthy donor, a procedure known as faecal microbiota transplantation (FMT). 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. 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 (Estimated): 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: Sidsel Støy, PhD; Phone Number: +4561664565; Email: sidsel.stoy@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

Description

Inclusion Criteria:

• Age 18-75 years
• Liver cirrhosis with Child-Pugh ≤ 12
• Acute decompensation requiring intervention (ascites, gastrointestinal bleeding, infections leading to progressive liver failure, overthepatic encephalopathy, alcoholic hepatitis)

Exclusion Criteria:

• More than one organ failure defined by CLIF-SOFA score
• Untreated malignancy apart from non-melanoma skin cancer
• Untreated viral hepatitis
• HIV
• Inflammatory bowel disease
• Celiac disease
• Clostridioides Difficile infection
• 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 new episode of acute decompensation requiring intervention in FMT 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 two groups, hazard ratios will be calculated.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death or new episode of acute decompensation requiring intervention in FMT versus placebo-treated patients at 3 months and 6 months of follow-up.	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 two groups, hazard ratios will be calculated.	3 months, 6 months
Change in disease severity in FMT- versus placebo-treated patients.	The disease severity will be measured with Model for Endstage Liver Disease (MELD) (range 6-40). A high score reflects poor prognosis.	3 months, 6 months, 1 year.
Change in disease severity in FMT- versus placebo-treated patients.	The disease severity will be measured with Child-Pugh score (range 5-15). A high score reflects poor prognosis.	3 months, 6 months, 1 year.
Change in disease severity in FMT- versus placebo-treated patients.	The disease severity will be measured with CliF-C Acute decompensation scores (range 0-18). A high score reflects poor prognosis.	3 months, 6 months, 1 year.
Change in metabolic liver function in FMT- versus placebo-treated patients.	The metabolic liver function will be measured by the aminopyrine breath test	3 months, 6 months, 1 year.
Change in liver stiffness in FMT- versus placebo-treated patients.	Liver stiffness will be measured by liver elastography.	3 months, 6 months, 1 year.
Change in the Liver Frailty Index in FMT- versus placebo-treated patients.	The Liver Frailty index (grip strength, chair stands, and balance testing) will be calculated and the index will be compared between the treatment groups. A higher LFI indicates more frailty.	3 months, 6 months, 1 year.
Change in body composition in FMT- versus placebo-treated patients.	Body composition will be measured by bioimpedance.	3 months, 6 months, 1 year.
Change in cognitive function in FMT- versus placebo-treated patients.	The cognitive function will be measured with the portosystemic encephalopathy syndrome test.	3 months, 6 months, 1 year.
Number of new decompensations and deaths during follow-up in the FMT versus the placebo-treated patients.	Incidence rates will be compared between the groups.	1 year
Time to death in FMT versus placebo-treated patients. -treated patients at 3 months and 6 months of follow-up.	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 two groups, hazard ratios will be calculated.	1 year, 6 months, 3 months
Change in gut microbiota beta-diversity (Bray-Curtis index) during one year in FMT versus placebo-treated patients by shotgun metagenomic 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, 6 months, 3 months
Change in plasma concentration of gut translocation markers; lipopolysaccharide binding protein, soluble CD14, fatty acid binding protein 1 during one year in FMT 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, 6 months, 3 months
Change in plasma and stool 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 and stool samples collected at baseline and at follow-up visits, we will measure these plasma proteins by luminex.	1 year, 6 months, 3 months
Change in cognitive function as measured by continuous reaction time in FMT- versus placebo-treated patients.	The cognitive function will be measured with continuous reaction time.	3 months, 6 months, 1 year.
Change in quality adjusted life years (QALY´s) to evalute health care related costs in FMT- versus placebo-treated patients	By using the quality-of-life questionnaire (EQ-5D-5L) a single index will be calculated and used to calculate QALY's.	1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): 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): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 21, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Ascites; Gastrointestinal bleeding; Hepatic encephalopathy; Hepatorenal syndrome; Alcoholic hepatitis; Spontaneous bacterial peritonitis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; 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
• product manufactured in and exported from the U.S.: No