Liver Cirrhosis
Conditions
Keywords
Hepatic encephalopathy, Ascites, Gastrointestinal bleeding, Spontaneous bacterial peritonitis, Hepatorenal syndrome, Alcoholic hepatitis
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.
Interventions
BIOLOGICALFaecal microbiota transplantation
All participant will receive three applications of either FMT or placebo and afterwards followed for 1 year.
BIOLOGICALPlacebo
Placebo
Sponsors
Aarhus University Hospital
Aalborg University Hospital
Odense University Hospital
Hvidovre University Hospital
Aalborg University
Esbjerg Hospital - University Hospital of Southern Denmark
Sjælland University Hospital
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to death or new episode of acute decompensation requiring intervention in FMT versus placebo-treated patients. | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of new decompensations and deaths during follow-up in the FMT versus the placebo-treated patients. | 1 year | Incidence rates will be compared between the groups. |
| Time to death in FMT versus placebo-treated patients. -treated patients at 3 months and 6 months of follow-up. | 1 year, 6 months, 3 months | 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. |
| Change in gut microbiota beta-diversity (Bray-Curtis index) during one year in FMT versus placebo-treated patients by shotgun metagenomic sequencing. | 1 year, 6 months, 3 months | 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 versus placebo-treated patients by ELISA. | 1 year, 6 months, 3 months | In blood samples collected at baseline and at follow-up visits, we will measure these plasma proteins by ELISA. |
| 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. | 1 year, 6 months, 3 months | In blood and stool samples collected at baseline and at follow-up visits, we will measure these plasma proteins by luminex. |
| Change in disease severity in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | The disease severity will be measured with Model for Endstage Liver Disease (MELD) (range 6-40). A high score reflects poor prognosis. |
| 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. | 3 months, 6 months | 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. |
| Change in liver stiffness in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | Liver stiffness will be measured by liver elastography. |
| Change in the Liver Frailty Index in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | 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. |
| Change in body composition in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | Body composition will be measured by bioimpedance. |
| Change in cognitive function as measured by continuous reaction time in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | The cognitive function will be measured with continuous reaction time. |
| Change in cognitive function in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | The cognitive function will be measured with the portosystemic encephalopathy syndrome test. |
| Change in quality adjusted life years (QALY´s) to evalute health care related costs in FMT- versus placebo-treated patients | 1 year | By using the quality-of-life questionnaire (EQ-5D-5L) a single index will be calculated and used to calculate QALY's. |
| Change in metabolic liver function in FMT- versus placebo-treated patients. | 3 months, 6 months, 1 year. | The metabolic liver function will be measured by the aminopyrine breath test |
Countries
Denmark
Contacts
Primary ContactKaren Louise Thomsen, PhD
Backup ContactSidsel Støy, PhD
Outcome results
None listed