MASLD steatotic liver disease
Conditions
Interventions
This study includes two non-pharmacological interventions: a nutritional challenge and a gutmicrobiota-targeted intervention.Lyophilized Fecal Microbiota Transplantation (LFMT):
Participants will be r
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Age 18–70 yearsClinical diagnosis of MASLD, based on imaging (e.g. ultrasound, Fibroscan (CAP), MRI-PDFF) and/or histology within the past 12 monthsPresence of at least one component of metabolic dysfunction (e.g. type 2 diabetes, obesity [BMI =28 kg/m²], hypertension, or dyslipidemia)Willing and able to provide written informed consentFluency in Dutch or EnglishEligible for deep sedation and endoscopy, as determined by clinical assessmentWilling and able to store study capsules at -20°C and adhere to daily oral intake for 4 weeks
Exclusion criteria
Exclusion criteria: Patients with advances fibrosis based on either liver biopsies (F3/F4) or a non-invasive test: FIB-4 = 2.67, or fibroscan values = 12.5 kPa. Significant alcohol consumption within 12 months prior to screening (>14 g/day for women, >21 g/day for men)Cirrhosis (clinical, histological, or radiologic evidence)Active hepatitis B or C infectionPortal hypertensionAutoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, Wilson’s disease, alpha-1-antitrypsin deficiency, or hemochromatosisHistory of liver transplantation or current listing for transplantationUse of antibiotics, prebiotics, probiotics, or synbiotics within 3 months prior to randomizationUse of tamoxifen, methotrexate, or amiodaroneActive treatment with GLP-1 receptor agonistsPlanned or prior bariatric surgeryKnown bleeding disorder or contraindications to biopsy (INR >1.4, platelets <100 × 10?/L)Use of antiplatelet or anticoagulant therapy that cannot be safely interruptedMajor cardiovascular event within 6 months prior to screening (e.g. myocardial infarction, stroke)Active or recent history of malignancy (except adequately treated in situ carcinoma or non-melanoma skin cancer)Known immunodeficiency (e.g. HIV with CD4 <240 cells/µL, chemotherapy within past 6 months)Scheduled major surgery during the study periodPregnant or breastfeedingAny other condition that, in the opinion of the investigator, may compromise patient safety or protocol adherenceParticipation in another clinical trial within the past 30 days
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint changes hepatic and small intestinal biopsy transcriptomic profiles in the fasting and postprandial state using single-nuclei RNA (spatial) sequencing of EUS-guided liver biopsies in relation to bileacid kinetics in patients with MASLD, assessed before and after a 4-week intervention of (small intestinal microbiota altering) LFMT or placebo capsules. Bile acid concentrations will be measured in portal vein, hepatic vein, and peripheral blood samples, collected in both fasting and postprandial states. The analysis will focus on how LFMT modulates postprandial bile acid dynamics and how these changes relate to hepatic and small intestinal gene expression patterns. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints are alterations in (small) intestinal microbiota composition and their related plasma metabolites in relation to liver histology with abovementioned parameters. | — |
Countries
Netherlands
Contacts
Public ContactM Nieuwdorp
Amsterdam UMC
Outcome results
None listed