non-alcoholic fatty liver disease non-alcoholic steatohepatitis
Conditions
Interventions
Participants will either receive 3x 21 LFMT capsules on 1 day and daily 2
LFMT-capsules, or the same amount of placebo capsules.
All participants will daily ingest 10^9 A. soehngenii CH-106 cells, 1
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - age 18-75 years - biopsy-proven NASH obtained up to 32 weeks before screening: SAF Steatosis score >=1, Activity >=2, Fibrosis
Exclusion criteria
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 units/day for females and more than 3 units/day for males, on average) - 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 - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement of liver histology in subjects with NASH and fibrosis stage 0-3, with improvement defined as reduction of steatohepatitis by >=1 SAF-A point and no worsening of liver fibrosis, or improvement in >= 1 stage liver fibrosis and no worsening of steatohepatitis. | — |
Secondary
| Measure | Time frame |
|---|---|
| - non-invasive outcomes of NAFLD, i.e. multiparametric MRI of liver and surrounding subcutaneous adipose tissue (MRI-PDFF, MR elastography, corrected T1), FibroScan Elastography and Controlled Attenuation Parameters, and plasma panel Enhanced Liver Fibrosis (ELF) panel, and plasma Pro-C3 concentrations. - liver gene expression profile: lipogenic, inflammatory and fibrogenic pathways - Liver pathology, histopathological features, immunofluorescence and assessment of pathophysiological proteins - blood markers of NAFLD and metabolic syndrome, namely: liver enzymes (i.e. alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP)), inflammatory blood markers (i.e. leukocytes, monocytes, CRP, Il-1(β), Il-6, Il-11, Il-17, Il-32, TNF-a, IFN-γ, other cytokines), SCFA (i.e. propionate, butyrate, acetate), lactate, lipids (i.e. LDL, HDL, triglycerides, total cholesterol), FGF21, adiponectin, leptin, lipopolysaccharides and zonulin, and metabolomic and lipodomic panels. - fecal microbiota composition, microbiome read outs (composition, engraftment, strain tracking) en metabolites, fecal albumin. - glycemic control, insulin resistance, HOMA-index (HOMA-IR), body weight/BMI, waist circumference and percentage body fat - MetSy criteria / % - quality of life (general (SF36) and NAFLD/NASH-specific (CDLQ-NAFLD)). Other study parameters - BMI - Waist circumference - Percentage body fat - Comorbidities (e.g. diabetes) - Smoking, yes/no - Alcohol intake - Polypharmacy (defined as chronic use of >= 5 different medications) - Daily caloric intake - Daily fat consumption | — |
Countries
Netherlands
Outcome results
None listed