Synbiotics and Fecal Microbiota Transplantation to Treat Non-Alcoholic Steatohepatitis

NL81001.018.22

The goal of this clinical trial is to investigate the therapeutic potential of A. soehngenii and pasteurized A. muciniphila combined with B. animalis subsp. lactis and fructo-oligosaccharides with and without conditioned vegan lyophilized fecal microbiota transplantation capsules to reduce NASH in patients with fibrotic NASH. The main questions to answer are: 1. Can NASH be treated by altering the gut microbiota using LFMT capsules? 2. Can NASH be treated using a syntrophic cocktail of synbiotics and will these strains strengthen the effect of FMT? 3. What are the underlying mechanism by which the aforementioned treatments attenuate NASH? Participants will be treated with FMT-capsules or placebo, and all participants will receive a cocktail of 3 strains of probiotics and one type of prebiotic.

2023-03-17

2025-02-20

2025-08-20

Recruiting

Early phase I

48

Inclusion Criteria: * biopsy-proven NASH obtained up to 32 weeks before screening: SAF Steatosis score ≥1, Activity ≥2, Fibrosis \<4; 50% of participants should at least have NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on tandem reading of two expert liver pathologists * fluency in Dutch or English * participants should be able to understand the information and give informed consent Exclusion Criteria: * Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year before screening (significant alcohol consumption is defined as more than 2 international units/day for females and more than 3 international units/day for males, on average; 1 international unit contains ±14 grams of alcohol) * liver cirrhosis or hepatocellular carcinoma * hepatitis B and/or C * auto-immune hepatitis * Wilson's disease * primary sclerosing cholangitis * primary biliary cholangitis * alpha-1-antitripsine deficiency and hemochromatosis * history of liver transplant, current placement on a liver transplant list * use of pre-, pro- or synbiotics * use of systemic antibiotics 3 month prior to randomization * use of tamoxifen, methotrexate or amiodarone * prior or planned bariatric surgery * active GLP-1 receptor agonist treated diabetes mellitus * bleeding disorder * International normalized ratio (INR) of prothrombin time \>1.4 or platelet count \<100 109/L at screening * anti-platelet/coagulant therapy use which cannot be temporarily discontinued * any major cardiovascular event within 6 months prior to screening (e.g. myocardial infarction, cerebrovascular accident) * prolonged compromised immunity (e.g. recent cytotoxic chemotherapy, HIV-infection with a CD4 count \< 240) * active or prior history of invasive malignancy (except for curatively treated in situ carcinomas \[e.g., cervix\] or non-melanoma skin cancer) unless a complete remission was achieved * surgery scheduled for the trial duration period, except for minor surgical procedures, in the opinion of the investigator * pregnant or nursing women * any condition which, in the investigator's opinion, might jeopardize participants' safety or compliance with the protocol * participation in another concomitant clinical trial.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomized placebo-controlled trial', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'maskingDescription': 'Doubleblind', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 48, 'type': 'ESTIMATED'}}

2023-04-20