Fecal Microbiome Transplantation in Cirrhosis. Randomized, Double-blinded, Placebo-Controlled trial in patients with decompensated cirrhosis.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Consorcio Centro De Investigacion Biomedica En Red

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

4 Jul 2025 → ongoing

Decision date (initial)

2025-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Instituto de Salud Carlos III and European Union Funds - Next Generation EU

External identifiers

EU CT number

2023-509151-13-00

ClinicalTrials.gov

NCT06533852

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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.

Secondary objectives 15

1. To analyze the impact of FMT in survival, assessed by the time to transplant-free survival and the incidence of mortality at different time points during the study period.
2. To assess the efficacy of FMT in the development/worsening of complications of cirrhosis during the study period.
3. To evaluate the effect of FMT in the frequency of hospital admissions due to complications of cirrhosis during the study period.
4. To study the impact of FMT in the incidence and severity of ACLF, as assessed by number and types of organ failures.
5. To analyze the effect of FMT on systemic inflammatory response, as estimated by measurement of a large array of inflammatory cytokines during the study period. Phenotype and function of peripheral blood mononuclear cells (PBMCs) will be analyzed during the study period.
6. To evaluate the effect of FMT in plasma and urine levels of biomarkers during the study period.
7. To evaluate the effects of FMT on systemic hemodynamics and vasoactive hormones during the study period.
8. To study the effect of FMT in blood levels of bacterial DNA and/or bacterial products during the study period.
9. To assess the effect of FMT in liver function, evaluated by MELD score, CLIF-C AD score and Child-Pugh Score during the study period.
10. To evaluate the effect of FMT in microbiome (saliva and fecal) composition at different time points during the study period.
11. To evaluate the impact of FMT on portal hypertension assessed by changes in hepatic venous pressure gradient (HVPG).
12. To analyze the impact of FMT in quality of life, functional assessment and minimal hepatic encephalopathy during study period, as assessed by CLDQ (Chronic Liver Disease Questionnaire), Liver Frailty score and PHES (Psychometric Hepatic Encephalopathy Score) questionnaires, respectively.
13. To study the effect of FMT in amount of alcohol consumption and patterns of consumption.
14. To study the impact of FMT in changes in electrocardiogram (ECG).
15. Type and severity of treatment-related adverse events during the study period.

Conditions and MedDRA coding

Decompensated cirrhosis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥ 18 years old.
2. 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).
3. Child-Pugh B or C patients (7- up to 12 points).
4. 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.

Exclusion criteria 20

1. Previous history of gastrointestinal surgery or colorectal cancer.
2. Patients with previous history of intestinal obstruction or those who are at increased risk of this complication.
3. Active Clostridium Difficile infection.
4. Patients on treatment with non-selective beta-blockers for <3 month or without stable doses.
5. Patients on treatment with any immunosuppressive drugs.
6. Patients on antiviral therapy for HCV or those who have received it within the last 12 months.
7. Patients on antiviral therapy for HBV therapy for < 12 months.
8. 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.
9. 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.
10. Patients with ACLF according to the criteria published by Moreau et al.
11. Severe alcoholic hepatitis requiring corticosteroid therapy (MELD > 20) in the last 6 months.
12. Patients with active alcohol consumption of more than 21 units per week.
13. HIV infection.
14. 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.
15. Patients with current extra hepatic malignancies including solid tumors and hematologic disorders.
16. Patients with previous organ transplantation.
17. Pregnancy or breastfeeding.
18. Patients included in other clinical trials in the month before inclusion.
19. 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.
20. Refusal to give informed consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 15

1. Time to transplant-free survival and mortality rates at month 1, month 3, month 6 and month 12.
2. 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.
3. Frequency of hospital admissions due to complications of cirrhosis assessed at baseline, 1 month, 3 months, 6 months and 12 months.
4. 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).
5. 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.
6. 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.
7. 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.
8. Changes from baseline in blood levels of bacterial DNA or bacterial products at 1 month, 3 months, 6 months and 12 months.
9. 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.
10. Analyze microbiome composition from saliva and stool by analysis of microbial genes at baseline, and months 1, 3 and 6.
11. Changes in HVPG from baseline to month 6.
12. 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.
13. Changes from baseline in AUDIT test at 3 months, 6 months and 12 months. Alcohol consumption will be monitorized by PETh measurement.
14. Changes in ACE score to assess the effect of FMT in ECG at screening, baseline and months 3, 6 and 12.
15. Proportion of patients and severity of treatment-related adverse events during the study period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Consorcio Centro De Investigacion Biomedica En Red

Sponsor organisation

Consorcio Centro De Investigacion Biomedica En Red

Address

Pab 11, Avenida Monforte De Lemos 3-5 Avenida Monforte De Lemos 3-5

City

Madrid

Postcode

28029

Country

Spain

Scientific contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Pere Ginès

Public contact point

Organisation

Consorcio Centro De Investigacion Biomedica En Red

Contact name

Pere Ginès

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications