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Faecal Microbiota Transplantation for Liver Cirrhosis (CHiFT)

Primary Purpose

Liver Cirrhosis

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Faecal microbiota transplantation
Placebo
Sponsored by
University of Aarhus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhosis focused on measuring Hepatic encephalopathy, Ascites, Gastrointestinal bleeding, Spontaneous bacterial peritonitis, Hepatorenal syndrome, Alcoholic hepatitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Hepatology and Gastroenterology, Aarhus University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Faecal microbiota transplantation

Placebo

Arm Description

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.

The placebo products is produced from a suspension of glycerol, saline and food colouring and cannot be distinguished from the active FMT products.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
May 26, 2021
Last Updated
November 3, 2021
Sponsor
University of Aarhus
Collaborators
Aarhus University Hospital, Aalborg University Hospital, Odense University Hospital, Hvidovre University Hospital, Aalborg University
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1. Study Identification

Unique Protocol Identification Number
NCT04932577
Brief Title
Faecal Microbiota Transplantation for Liver Cirrhosis
Acronym
CHiFT
Official Title
Faecal Microbiota Transplantation to Prevent Complications, Progression and Mortality of Liver Cirrhosis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2021 (Actual)
Primary Completion Date
May 31, 2026 (Anticipated)
Study Completion Date
May 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
Collaborators
Aarhus University Hospital, Aalborg University Hospital, Odense University Hospital, Hvidovre University Hospital, Aalborg University

4. Oversight

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

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis
Keywords
Hepatic encephalopathy, Ascites, Gastrointestinal bleeding, Spontaneous bacterial peritonitis, Hepatorenal syndrome, Alcoholic hepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Faecal microbiota transplantation
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The placebo products is produced from a suspension of glycerol, saline and food colouring and cannot be distinguished from the active FMT products.
Intervention Type
Biological
Intervention Name(s)
Faecal microbiota transplantation
Other Intervention Name(s)
FMT
Intervention Description
All participant will receive three applications of either FMT or placebo and afterwards followed for 1 year.
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Time to death or re-admission due to episode of acute decompensation in FMT treated versus placebo treated patients.
Description
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.
Time Frame
1 year
Title
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.
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change in gut microbiota beta-diversity (Bray-Curtis index, taxonomic abundance) during one year in FMT treated versus placebo treated patients by 16S sequencing.
Description
In stool and saliva samples collected before and at 5 time points following the intervention, we will measure the gut microbiota composition.
Time Frame
1 year
Title
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.
Description
In blood samples collected at baseline and at follow-up visits, we will measure these plasma proteins by ELISA.
Time Frame
1 year
Title
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.
Description
In blood samples collected at baseline and at follow-up visits, we will measure these plasma proteins by luminex.
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karen Louise Thomsen, PhD
Phone
+4526949260
Email
karethom@rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Lotte Lindgreen Eriksen
Phone
+4529279784
Email
lotter@clin.au.dk
Facility Information:
Facility Name
Department of Hepatology and Gastroenterology, Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen Louise Thomsen, PhD
Phone
+4526949260
Email
karethom@rm.dk

12. IPD Sharing Statement

Plan to Share IPD
No

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Faecal Microbiota Transplantation for Liver Cirrhosis

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