Actively Recruiting
A Prospective Multicenter International Randomized Controlled Trial Comparing Surgical and Medical Therapies in the Treatment of Advanced Metabolic Dysfunction Associated Steatohepatitis
Led by Ali Aminian · Updated on 2025-08-22
120
Participants Needed
22
Research Sites
30 weeks
Total Duration
On this page
Sponsors
A
Ali Aminian
Lead Sponsor
S
Sobia Laique, MD
Collaborating Sponsor
AI-Summary
What this Trial Is About
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD), is a common liver condition linked to obesity, diabetes, and cholesterol problems. It ranges from simple fat buildup in the liver to more serious conditions like metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and liver cancer. Patients with MASH also face risks of heart disease and death. Currently, no approved medications exist for MASH, and weight loss remains the primary treatment approach. This study compares two treatments for patients with obesity, MASH, and liver fibrosis: metabolic surgery or medical therapy using incretin-based drugs such as liraglutide, semaglutide, or tirzepatide. About 120 patients will be randomly assigned to one of these two groups and followed for two years. The surgical group will receive either Roux-en-Y gastric bypass or sleeve gastrectomy based on shared decisions with their medical team. The medical group will use one of the approved incretin-based medications, depending on availability and clinical suitability. Participants will undergo a liver biopsy at the start and after two years to assess changes in liver fibrosis and MASH status. Throughout the study, researchers will monitor weight loss, liver health, and quality of life. The main goal is to see if there is at least a one-stage improvement in liver fibrosis without worsening MASH. Safety, liver function, and treatment effects will be carefully tracked during the study period.
CONDITIONS
Brief Title
Fibrosis Lessens After Metabolic Surgery
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Candidate for general anesthesia
- Eligible for metabolic surgery based on ASMBS/IFSO 2022 guidelines
- Has insurance coverage for metabolic surgery (varies by country)
- Aged 18 to 75 years at informed consent
- BMI between 35 and 70 kg/m2 at first study visit
- FIB-4 index equal or greater than 1.3
- At least one advanced fibrosis indicator: LSM ≥12 kPa by FibroScan or similar tests, SWE, ARFI, MRE, or ELF score ≥9.8
- Patients with or without type 2 diabetes; diabetic patients must have stable anti-diabetic medication (excluding certain drugs) for at least 3 months and HbA1c ≤12%
- Stable weight with less than 10% loss in the 6 months before the study visit
- Ability and willingness to participate and provide informed consent
- Willingness to undergo liver biopsies at screening and after 2 years
- Negative urine pregnancy test for women of childbearing potential at screening and randomization
- Women of childbearing age must agree to reliable contraception for 2 years
You will not qualify if you...
- Other chronic liver diseases including hepatitis B or C, autoimmune liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, alpha-1-antitrypsin deficiency, hemochromatosis, drug-induced liver disease, bile duct obstruction, or liver cancer
- Weight change greater than 10% within 6 months prior to study visit
- Use of semaglutide, tirzepatide, or liraglutide within 90 days before study visit unless low dose with less than 10% weight loss
- Type 1 or autoimmune diabetes
- HIV infection
- Prior bariatric or metabolic surgery (except certain reversed procedures)
- Prior complex foregut surgery
- Surgery requiring general anesthesia within 1 month before consent
- Solid organ transplant history
- Severe lung or heart disease with specific criteria
- Recent heart attack, stroke, or heart surgery within 6 months
- Severe kidney disease or dialysis
- Large hiatal hernia (>7 cm)
- Crohn's disease
- Certain psychiatric disorders or recent substance abuse
- Pregnancy, breastfeeding, or inadequate contraception
- Recent cancer diagnosis except certain skin cancers
- Anemia with hemoglobin less than 9 g/dL
- Use of therapeutic anticoagulants
- Clotting disorders
- Life expectancy under 3 years
- Recent investigational therapy use
- Pancreatic disorders
- Concerning or uncontrolled thyroid disease
- History or evidence of serious liver complications or portal hypertension
- Significant alcohol use within 1 year prior
- Use of medications affecting liver fat within 3 months
- Elevated liver enzymes beyond set limits
- Recurrent major hypoglycemia
- Inability to safely undergo liver biopsy
- Other conditions posing undue risk or inability to consent
- Plans to move outside study location within 24 months
- Allergy to study medications
- Previous trial participation without proceeding
- Recent COVID-19 hospitalization
- Low platelet count or abnormal clotting tests
- Advanced liver disease scores or findings on endoscopy or imaging
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 2 years
Participants receive either metabolic surgery or incretin-based therapies for 2 years to treat metabolic dysfunction associated steatohepatitis and liver fibrosis.
Visits scheduled periodically throughout the 2 years depending on treatment group and clinical care
Duration - At 2 years after treatment start
Participants undergo a repeat liver biopsy after 2 years to assess treatment outcomes and effects on liver histology.
1 visit (in-person) for repeat liver biopsy
Trial Site Locations
Total: 22 locations
1
Banner Health Center
Phoenix, Arizona, United States, 85006
Not Yet Recruiting
2
Indiana University
Indianapolis, Indiana, United States, 46202
Not Yet Recruiting
3
Mayo Clinic
Rochester, Minnesota, United States, 55905
Not Yet Recruiting
4
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Actively Recruiting
5
Hospital Alemão Oswaldo Cruz
São Paulo, Brazil
Actively Recruiting
6
McGill University
Montreal, Canada
Not Yet Recruiting
7
Turku University Hospital
Turku, Finland
Not Yet Recruiting
8
Sri Aurobindo Institute of Medical Sciences
Indore, India
Not Yet Recruiting
9
The Digestive Health Institute
Mumbai, India
Not Yet Recruiting
10
University College Dublin
Dublin, Ireland
Not Yet Recruiting
11
Università Cattolica del Sacro Cuore
Milan, Italy
Not Yet Recruiting
12
Sapienza Università di Roma
Roma, Italy
Not Yet Recruiting
13
Kuwait University
Kuwait City, Kuwait
Not Yet Recruiting
14
Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Mexico City, Mexico
Not Yet Recruiting
15
Hospital Clínic Barcelona
Barcelona, Spain
Not Yet Recruiting
16
Linköping University
Linköping, Sweden
Not Yet Recruiting
17
Örebro University
Örebro, Sweden
Not Yet Recruiting
18
Clarunis Universitäres
Basel, Switzerland
Not Yet Recruiting
19
Hôpitaux universitaires de Genève
Geneva, Switzerland
Not Yet Recruiting
20
Nuffield Health Bristol Hospital
Bristol, United Kingdom
Not Yet Recruiting
21
King's College Hospital
London, United Kingdom
Not Yet Recruiting
22
Queen Mary University
London, United Kingdom
Not Yet Recruiting
Research Team
A
Awwab F Hammad, MD
C
Chytaine Hall
How is the study designed?
Study Type
INTERVENTIONAL
Masking
SINGLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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