Fecal Microbiome Transplantation in Cirrhosis. Randomized, Double-blinded, Placebo-Controlled trial in patients with decompensated cirrhosis.
- Conditions
- Decompensated cirrhosis
- Registration Number
- 2023-509151-13-00
- Brief Summary
To evaluate the efficacy of fecal microbiome trasplantation (FMT) in halting the progression of decompensated cirrhosis as assessed by the time to first incidence decompensated episode during study period.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised, recruitment pending
- Sex
- Not specified
- Target Recruitment
- 190
Age ≥ 18 years old.
Cirrhosis defined by standard clinical criteria, ultrasonographic findings and/or histology. Cirrhosis of any etiology may be included except from patients with cirrhosis due to autoimmune hepatitis, and patients with cirrhosis due to cholestatic liver disease can only be included in the study if they present clinical decompensation of cirrhosis (i.e. ascites).
Child-Pugh B or C patients (7- up to 12 points).
Women of child-bearing potential must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence (only if refraining from heterosexual intercourse during the period of twelve months of duration of the study). Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function.
Previous history of gastrointestinal surgery or colorectal cancer.
Patients with ACLF according to the criteria published by Moreau et al.
Severe alcoholic hepatitis requiring corticosteroid therapy (MELD > 20) in the last 6 months.
Patients with active alcohol consumption of more than 21 units per week.
HIV infection.
Patients with a history of significant extra hepatic disease with impaired short-term prognosis, including congestive heart failure New York Heart Association Grade III/IV, COPD GOLD >2, chronic kidney disease with serum creatinine >2mg/dL or under renal replacement therapy.
Patients with current extra hepatic malignancies including solid tumors and hematologic disorders.
Patients with previous organ transplantation.
Pregnancy or breastfeeding.
Patients included in other clinical trials in the month before inclusion.
Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.
Patients with previous history of intestinal obstruction or those who are at increased risk of this complication.
Refusal to give informed consent.
Active Clostridium Difficile infection.
Patients on treatment with non-selective beta-blockers for <3 month or without stable doses.
Patients on treatment with any immunosuppressive drugs.
Patients on antiviral therapy for HCV or those who have received it within the last 12 months.
Patients on antiviral therapy for HBV therapy for < 12 months.
Patients with hepatocellular carcinoma, except for patients with early HCC (BCLC-0 or BCLC-A) or patients with previous history of HCC and absence of recurrence 2 years after treatment.
Patients admitted to the hospital for acute decompensation of the disease. These patients could be included after discharged as long as they do not present any of the following events: a. Bacterial infection within 10 days before study inclusion. b. Gastrointestinal bleeding within 10 days before study inclusion. c. Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the New-Haven classification.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Efficacy of treatment in halting the progression of decompensated cirrhosis as assessed by time to first decompensation event (acute kidney injury (AKI), ascites, bacterial infection, gastrointestinal bleeding, Hepatic Encephalopathy (HE)) during the study period. Efficacy of treatment in halting the progression of decompensated cirrhosis as assessed by time to first decompensation event (acute kidney injury (AKI), ascites, bacterial infection, gastrointestinal bleeding, Hepatic Encephalopathy (HE)) during the study period.
- Secondary Outcome Measures
Name Time Method Time to transplant-free survival and mortality rates at month 1, month 3, month 6 and month 12. Time to transplant-free survival and mortality rates at month 1, month 3, month 6 and month 12.
Development/worsening of individual complications of cirrhosis (ascites, AKI, bacterial infections, gastrointestinal bleeding, HE) assessed at baseline, month 1, month 3, month 6 and month 12. Development/worsening of individual complications of cirrhosis (ascites, AKI, bacterial infections, gastrointestinal bleeding, HE) assessed at baseline, month 1, month 3, month 6 and month 12.
Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months and 12 months. Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months and 12 months.
Development of acute-on-chronic liver failure (ACLF) defined according to criteria by Moreau R, et al. (Time to first episode of ACLF; Total number of patients developing ACLF at month 3, month 6 and month 12; Severity of ACLF episodes based on ACLF grade and CLIF-C-ACLF score; Number and type of organ failures). Development of acute-on-chronic liver failure (ACLF) defined according to criteria by Moreau R, et al. (Time to first episode of ACLF; Total number of patients developing ACLF at month 3, month 6 and month 12; Severity of ACLF episodes based on ACLF grade and CLIF-C-ACLF score; Number and type of organ failures).
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 1 month, 3 months, 6 months and 12 months. PBMCs phenotype and function will be analysed by flow cytometry, functional analysis, and RNAseq single cell analysis at baseline, 1 month, 3 months, 6 months and 12 mo. 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 1 month, 3 months, 6 months and 12 months. PBMCs phenotype and function will be analysed by flow cytometry, functional analysis, and RNAseq single cell analysis at baseline, 1 month, 3 months, 6 months and 12 mo.
Changes from baseline in different plasma and urine prognostic biomarkers including, but not only, copeptin, NGAL, PD-L1, L-FABP, at 1 month, 3 months, 6 months, and 12 months. Changes from baseline in different plasma and urine prognostic biomarkers including, but not only, copeptin, NGAL, PD-L1, L-FABP, at 1 month, 3 months, 6 months, and 12 months.
Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma renin concentration and plasma copeptin at 1 month, 3 months, 6 months and 12 months. Changes from baseline in systemic hemodynamics and vasoactive hormones: plasma renin concentration and plasma copeptin at 1 month, 3 months, 6 months and 12 months.
Changes from baseline in blood levels of bacterial DNA or bacterial products at 1 month, 3 months, 6 months and 12 months. Changes from baseline in blood levels of bacterial DNA or bacterial products at 1 month, 3 months, 6 months and 12 months.
Changes from baseline in liver function, evaluated by MELD score, CLIF-AD score and Child Pugh Score at 1 month, 3 months, 6 months and 12 months. Changes from baseline in liver function, evaluated by MELD score, CLIF-AD score and Child Pugh Score at 1 month, 3 months, 6 months and 12 months.
Analyze microbiome composition from saliva and stool by analysis of microbial genes at baseline, and months 1, 3 and 6. Analyze microbiome composition from saliva and stool by analysis of microbial genes at baseline, and months 1, 3 and 6.
Changes in HVPG from baseline to month 6. Changes in HVPG from baseline to month 6.
The data obtained from CLDQ (Chronic Liver Disease Questionnaire), Liver Frailty Index and PHES (Psychometric Hepatic Encephalopathy Score) questionnaires to assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy at baseline, 3 months, 6 months and 12 months. The data obtained from CLDQ (Chronic Liver Disease Questionnaire), Liver Frailty Index and PHES (Psychometric Hepatic Encephalopathy Score) questionnaires to assess Quality of life, functional assessment and in Minimal Hepatic Encephalopathy at baseline, 3 months, 6 months and 12 months.
Changes from baseline in AUDIT test at 3 months, 6 months and 12 months. Alcohol consumption will be monitorized by PETh measurement. Changes from baseline in AUDIT test at 3 months, 6 months and 12 months. Alcohol consumption will be monitorized by PETh measurement.
Changes in ACE score to assess the effect of FMT in ECG at screening, baseline and months 3, 6 and 12. Changes in ACE score to assess the effect of FMT in ECG at screening, baseline and months 3, 6 and 12.
Proportion of patients and severity of treatment-related adverse events during the study period. Proportion of patients and severity of treatment-related adverse events during the study period.
Trial Locations
- Locations (8)
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitari Vall D Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Puerta De Hierro De Majadahonda
🇪🇸Madrid, Spain
Hospital Universitario Marques De Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Parc Tauli Hospital Universitari
🇪🇸Sabadell, Spain
Hospital Clinic De Barcelona
🇪🇸Barcelona, Spain
Hospital De La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon🇪🇸Madrid, SpainRafael Bañares CañizaresSite contact+34915868000rbanares@ucm.es