Clinical trial NCT04932577: Faecal Microbiota Transplantation for Liver Cirrhosis
Official title: Faecal Microbiota Transplantation to Prevent Complications, Progression and Mortality of Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Liver Cirrhosis
Keywords: Hepatic encephalopathy
Ascites
Gastrointestinal bleeding
Spontaneous bacterial peritonitis
Hepatorenal syndrome
Alcoholic hepatitis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Aalborg University Hospital
name: Odense University Hospital
name: Hvidovre University Hospital
name: Aalborg University
name: Esbjerg Hospital - University Hospital of Southern Denmark
name: Sjælland University Hospital
First posted: 2021-06-21
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to death or new episode of acute decompensation requiring intervention in FMT versus placebo-treated patients.
timeFrame: 1 year
Secondary outcomes:
measure: 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.
timeFrame: 3 months, 6 months
measure: Number of new decompensations and deaths during follow-up in the FMT versus the placebo-treated patients.
timeFrame: 1 year
measure: Time to death in FMT versus placebo-treated patients. -treated patients at 3 months and 6 months of follow-up.
timeFrame: 1 year, 6 months, 3 months
measure: Change in gut microbiota beta-diversity (Bray-Curtis index) during one year in FMT versus placebo-treated patients by shotgun metagenomic sequencing.
timeFrame: 1 year, 6 months, 3 months
measure: 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.
timeFrame: 1 year, 6 months, 3 months
measure: 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.
timeFrame: 1 year, 6 months, 3 months
measure: Change in disease severity in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in disease severity in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in disease severity in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in metabolic liver function in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in liver stiffness in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in the Liver Frailty Index in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in body composition in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in cognitive function as measured by continuous reaction time in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in cognitive function in FMT- versus placebo-treated patients.
timeFrame: 3 months, 6 months, 1 year.
measure: Change in quality adjusted life years (QALY´s) to evalute health care related costs in FMT- versus placebo-treated patients
timeFrame: 1 year
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Hepatology and Gastroenterology, Aarhus University Hospital
Study officials:
References: