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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
220
All participant will receive three applications of either FMT or placebo and afterwards followed for 1 year.
Placebo
Department of Hepatology and Gastroenterology, Aarhus University Hospital
Aarhus, Denmark
RECRUITINGTime 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.
Time frame: 1 year
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.
Time frame: 3 months, 6 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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In blood samples collected at baseline and at follow-up visits, we will measure these plasma proteins by ELISA.
Time frame: 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.
Time frame: 1 year, 6 months, 3 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 3 months, 6 months, 1 year.
Change in liver stiffness in FMT- versus placebo-treated patients.
Liver stiffness will be measured by liver elastography.
Time frame: 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.
Time frame: 3 months, 6 months, 1 year.
Change in body composition in FMT- versus placebo-treated patients.
Body composition will be measured by bioimpedance.
Time frame: 3 months, 6 months, 1 year.
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.
Time frame: 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.
Time frame: 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.
Time frame: 1 year