RecruitingPhase 2NCT05821010

Synbiotics and Fecal Microbiota Transplantation to Treat Non-Alcoholic Steatohepatitis

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Enrollment

48 participants

Start Date

Mar 17, 2023

Study Type

INTERVENTIONAL

Conditions

Non-Alcoholic Fatty Liver Disease Non Alcoholic Steatohepatitis Microbiome Fecal Microbiota Transplantation Probiotics FMT Prebiotics

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria3

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 Criteria24

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.