Using gut microbiota treatments to reduce liver disease

Synbiotics and Fecal Microbiota Transplantation to Treat Non-Alcoholic Steatohepatitis

This study is testing whether a combination of probiotics, prebiotics, and fecal microbiota transplants can help people with liver disease feel better and improve their liver health.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (other)
• Drugs / interventions: chemotherapy, methotrexate
• Locations: 1 site (Amsterdam, North Holland)
• Trial ID: NCT05821010 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of a combination of specific probiotics and prebiotics, along with fecal microbiota transplantation (FMT) capsules, to treat patients with non-alcoholic steatohepatitis (NASH). Participants will receive either the active treatment or a placebo in a double-blind, randomized design. The study aims to determine if altering gut microbiota can improve liver health and to explore the mechanisms behind these treatments. Patients will be monitored over a period of 16 weeks to assess changes in their condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with biopsy-proven NASH and specific fibrosis stages.

Not a fit: Patients with liver cirrhosis, significant alcohol consumption, or other specified liver diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel approach to managing and potentially reversing liver damage in patients with NASH.

How similar studies have performed: While the approach of using gut microbiota for liver disease is emerging, this specific combination of treatments is novel and has not been extensively tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Amsterdam, North Holland

• Amsterdam UMC — Amsterdam, North Holland, Netherlands (RECRUITING)

Study contacts

• Principal investigator: A.G. Holleboom, MD, PhD — Amsterdam UMC
• Study coordinator: Quinten Augustijn, MD

Conditions: Non Alcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease, Fecal Microbiota Transplantation, FMT, Prebiotics, Probiotics, Microbiome, Intestinal Microbiome