Fecal Microbiome Transplantation in Cirrhosis: Trial in Patients With Decompensated Cirrhosis
NCT Number: NCT06533852
Acronym: LiverGut
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Decompensated Cirrhosis
Interventions: DRUG: Fecal Microbiome Transplantation (FMT)|OTHER: FMT Placebo
Sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 190
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-12
Completion Date: 2028-05

Summary:
This is a phase III, multicenter, double-blind, placebo-controlled, randomized clinical trial to evaluate the safety and efficacy of Fecal Microbiota Transplantation (FMT) from healthy subjects to patients with decompensated cirrhosis.

Primary Outcome Measures: Efficacy of treatment in halting the progression of decompensated cirrhosis., Assessed by time to first decompensation event (acute kidney injury (AKI), ascites, bacterial infection, gastrointestinal bleeding, HE)., Screening to month 12.
Secondary Outcome Measures: Time to transplant-free survival, Assessed by transplant-free survival, At month 1, month 3, month 6 and month 12|Mortality rates, Assessed by mortality rates, At month 1, month 3, month 6 and month 12|Rate of patients developing/ worsening individual complications of cirrhosis., Assessed by ascites, acute kidney injury, bacterial infections, gastrointestinal bleeding and hepatic encephalopathy., At baseline, month 1, month 3, month 6 and month 12.|Frequency of hospital admissions due to complications of cirrhosis., Assessed by hospital admissions due to complications of cirrhosis., At baseline, 1 month, 3 months, 6 months and 12 months.|Development of acute-on-chronic liver failure (ACLF), Assessed by time to first episode of ACLF, At baseline, 1 month, 3 months, 6 months and 12 months.|Development of acute-on-chronic liver failure (ACLF), Assessed by total number of patients developing ACLF, At month 3, month 6 and month 12.|Development of acute-on-chronic liver failure (ACLF), Assessed by severity of ACLF episodes based on ACLF grade (from grade 1 to grade 3) and CLIF-C-ACLF score, At baseline, 1 month, 3 months, 6 months and 12 months.|Development of acute-on-chronic liver failure (ACLF), Assessed by number and type of organ failures, At baseline, 1 month, 3 months, 6 months and 12 months.|Changes from baseline in systemic inflammatory response., Evaluated by measurement in a large array of plasma cytokine levels including, but not limited to TNFα, IL-6, IL8, IL-10, IL-1β, IFN-ɣ, G-CSF, VCAM, VEGF, as well as an oxidized form of albumin, human nonmercaptalbumin-2 (HNA2)., At baseline, 1 month, 3 months, 6 months and 12 months.|PBMCs phenotype and function., Analysed by flow cytometry, functional analysis, and RNAseq single cell analysis., At baseline, 1 month, 3 months, 6 months and 12 months.|Changes from baseline in different plasma and urine prognostic biomarkers., Measurated by different plasma and urine prognostic biomarkers including, but not only, copeptin, NGAL, PD-L1, L-FABP., At baseline, 1 month, 3 months, 6 months, and 12 months.|Changes from baseline in systemic hemodynamics and vasoactive hormones., Measurated by systemic hemodynamics and vasoactive hormones: plasma renin concentration and plasma copeptin., At baseline, 1 month, 3 months, 6 months and 12 months.|Changes from baseline in blood levels of bacterial DNA or bacterial products., Measurated by blood levels of bacterial DNA or bacterial products., At baseline, 1 month, 3 months, 6 months and 12 months.|Changes from baseline in liver function., Evaluated by MELD (Model for End-stage Liver Disease) score., At baseline, 1 month, 3 months, 6 months and 12 months.|Changes from baseline in liver function., Evaluated by CLIF-AD score., At baseline, 1 month, 3 months, 6 months and 12 months.|Changes from baseline in liver function., Evaluated by Child Pugh Score.(from 1 point to 15 points), At baseline, 1 month, 3 months, 6 months and 12 months.|Analyze microbiome composition from saliva and stool., Measurated by analysis of microbial genes., At baseline, and months 1, 3 and 6.|Changes in hepatic venous pressure gradient (HVPG) from baseline., Measurated by the hepatic venous pressure gradient., At baseline and month 6.|Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy., Evaluated with data obtained from CLDQ (Chronic Liver Disease Questionnaire) questionnaire., At baseline, 3 months, 6 months and 12 months.|Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy., Evaluated with data obtained from Liver Frailty Index., At baseline, 3 months, 6 months and 12 months.|Assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy., Evaluated with data obtained from PHES (Psychometric Hepatic Encephalopathy Score) questionnaire., At baseline, 3 months, 6 months and 12 months.|Changes from baseline in AUDIT test., Evaluated from AUDIT test, AUDIT test at baseline, 3 months, 6 months and 12 months|Changes from baseline in alcohol consumption., Evaluated from PETh measurament., PETh measurament test at baseline, 1 month, 3 months, 6 months and 12 months.|Assess the effect of FMT in ECG (Electrocardiogram)., Evaluated by changes in ACE score., At screening, baseline and months 3,6 and 12.|Proportion of patients with treatment-related adverse events., Evaluated by treatment-related adverse events., Screening to month 12.|Proportion of patients with severe treatment-related adverse events., Evaluated by treatment-related adverse events., Screening to month 12.