protocolSection identificationModule nctId: NCT06374875, orgStudyIdInfo id: 24-213, briefTitle: Fibrosis Lessens After Metabolic Surgery, acronym: FLAMES, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-05-01, primaryCompletionDateStruct date: 2029-05-31, completionDateStruct date: 2029-12-31, studyFirstPostDateStruct date: 2024-04-19, lastUpdatePostDateStruct date: 2024-04-19, sponsorCollaboratorsModule leadSponsor name: Ali Aminian, class: OTHER, descriptionModule briefSummary: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), a major global public health concern, is commonly associated with obesity, diabetes, and dyslipidemia. MASLD is currently the most common cause of chronic liver disease affecting about 80% of people with obesity, ranging from simple fat deposits in the liver to Metabolic Dysfunction-Associated Steatohepatitis (MASH), cellular injury, advanced fibrosis, cirrhosis, or hepatocellular carcinoma. Patients with MASH are also at risk for cardiovascular disease and mortality. There is no universally approved medication for MASH. Weight loss remains the cornerstone of MASH treatment.Patients meeting the inclusion and exclusion criteria and who give informed consent will be enrolled in the trial and undergo the baseline liver biopsy (if none available). Approximately 120 patients with MASH and liver fibrosis (F1-F4 in baseline liver biopsy) will be randomized in a 1:1 ratio to metabolic surgery or medical treatment (incretin-based therapies ± other medical therapies for MASH) and followed for 2 years at which time a repeat liver biopsy will be performed for the assessment of the primary end point., conditionsModule conditions: Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD), conditions: Non-Alcoholic Fatty Liver Disease, conditions: Metabolic Dysfunction-Associated Steatohepatitis (MASH), conditions: Liver Fibrosis, conditions: Obesity, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: RANDOMIZED, interventionModel: PARALLEL, interventionModelDescription: Patients will be randomized in a 1:1 ratio into 1 of the 2 arms using a computer-generated randomization plan, stratified to ensure that there are equal number of patients with/without T2DM and with/without F4 (cirrhosis) according to the baseline liver biopsy in each treatment group (surgical group vs non-surgical group). The participant sites are regrouped into three geographic regions. All patients in each region will be randomized separately to have equal number of patients with/without T2DM and with/without F4 in each treatment group in each region., primaryPurpose: TREATMENT, maskingInfo masking: SINGLE, maskingDescription: Patients and investigators will not be blinded to treatment assignment. The treatment assignment will remain unknown until the patient is randomized after meeting all eligibility requirements.Pathologists who report the liver biopsies (to assess the primary end point of study) are blinded to treatment assignment, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 120, type: ESTIMATED, armsInterventionsModule interventions name: Metabolic surgery, interventions name: Incretin-Based Therapy, outcomesModule primaryOutcomes measure: Improvement of at least 1 fibrosis stage of the Kleiner fibrosis classification and no worsening of MASH in the repeat liver biopsy., secondaryOutcomes measure: MASH resolution in the repeat liver biopsy, secondaryOutcomes measure: MASH resolution and fibrosis improvement in the repeat liver biopsy, secondaryOutcomes measure: Fibrosis progression in the repeat liver biopsy, secondaryOutcomes measure: Average Weight loss percentage, secondaryOutcomes measure: Disease-specific Quality of Life (QoL), otherOutcomes measure: MASLD-related histopathologic end points, otherOutcomes measure: MASLD-related laboratory end points, otherOutcomes measure: MASLD-related liver scan end points, otherOutcomes measure: MASLD-related clinical end points, otherOutcomes measure: Achieved Weight-loss proportions, otherOutcomes measure: Weight change (kg), otherOutcomes measure: BMI change (kg/m^2), otherOutcomes measure: Excess weight loss, %, otherOutcomes measure: Change in waist circumference, cm, otherOutcomes measure: Systolic blood pressure trends, mmHg, otherOutcomes measure: Mean and change from baseline in lipid panel, mg/dl, otherOutcomes measure: Changes in glucose hemostasis markers, otherOutcomes measure: Percentage of patients with T2DM meeting predefined HbA1c targets, otherOutcomes measure: Changes in inflammatory markers, CRP mg/L, otherOutcomes measure: Change in cardiovascular and diabetes medications, otherOutcomes measure: SF-Bari Score, otherOutcomes measure: Quality of life end points, otherOutcomes measure: Safety end points, eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 70 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Banner Health Center, city: Phoenix, state: Arizona, zip: 85006, country: United States, contacts name: Farah Husain, MD, role: CONTACT, email: Farah.husain@bannerhealth.com, geoPoint lat: 33.44838, lon: -112.07404, locations facility: Indiana University, city: Indianapolis, state: Indiana, zip: 46202, country: United States, contacts name: Dimitrios Stefanidis, MD, PhD, role: CONTACT, email: dstefanidis@iuhealth.org, geoPoint lat: 39.76838, lon: -86.15804, locations facility: Mayo Clinic, city: Rochester, state: Minnesota, zip: 55905, country: United States, contacts name: Omar Ghanem, MD, role: CONTACT, email: ghanem.omar@mayo.edu, geoPoint lat: 44.02163, lon: -92.4699, locations facility: Cleveland Clinic, city: Cleveland, state: Ohio, zip: 44195, country: United States, contacts name: Ali Aminian, MD, role: CONTACT, email: aminiaa@ccf.org, geoPoint lat: 41.4995, lon: -81.69541, locations facility: Hospital Alemão Oswaldo Cruz, city: São Paulo, country: Brazil, contacts name: Ricardo Cohen, MD, role: CONTACT, email: ricardo.cohen@haoc.com.br, geoPoint lat: -23.5475, lon: -46.63611, locations facility: McGill University, city: Montréal, country: Canada, contacts name: Amin Andalib, MDCM, MSc, role: CONTACT, email: amin.andalib@mcgill.ca, geoPoint lat: 45.50884, lon: -73.58781, locations facility: Turku University Hospital, city: Turku, country: Finland, contacts name: Paulina Salminen, MD, PhD, role: CONTACT, email: paulina.salminen@tyks.fi, geoPoint lat: 60.45148, lon: 22.26869, locations facility: Sri Aurobindo Institute of Medical Sciences, city: Indore, country: India, geoPoint lat: 22.71792, lon: 75.8333, locations facility: The Digestive Health Institute, city: Mumbai, country: India, geoPoint lat: 19.07283, lon: 72.88261, locations facility: University College Dublin, city: Dublin, country: Ireland, contacts name: Helen Heneghan, MB BCh BAO, PhD, role: CONTACT, email: helen.heneghan@ucd.ie, geoPoint lat: 53.33306, lon: -6.24889, locations facility: Università Cattolica del Sacro Cuore, city: Milan, country: Italy, contacts name: Geltrude Mingrone, M.D. PhD, role: CONTACT, email: geltrude.mingrone@unicatt.it, geoPoint lat: 45.46427, lon: 9.18951, locations facility: Sapienza Università di Roma, city: Roma, country: Italy, contacts name: Giovanni Casella, MD, role: CONTACT, email: giovanni.casella@uniroma1.it, geoPoint lat: 41.89193, lon: 12.51133, locations facility: Kuwait University, city: Kuwait, country: Kuwait, geoPoint lat: 29.36972, lon: 47.97833, locations facility: Instituto Nacional de Ciencias Médicas y Nutrición Salvador, city: Mexico City, country: Mexico, contacts name: Mauricio Sierra, MD, role: CONTACT, geoPoint lat: 19.42847, lon: -99.12766, locations facility: Hospital Clínic Barcelona, city: Barcelona, country: Spain, geoPoint lat: 41.38879, lon: 2.15899, locations facility: Linköping University, city: Linköping, country: Sweden, geoPoint lat: 58.41086, lon: 15.62157, locations facility: Örebro University, city: Örebro, country: Sweden, contacts name: Erik Stenberg, MD, PhD, role: CONTACT, email: erik.stenberg@regionorebrolan.se, geoPoint lat: 59.27412, lon: 15.2066, locations facility: Clarunis Universitäres, city: Basel, country: Switzerland, contacts name: Ralph Peterli, Dr. med, role: CONTACT, email: ralph.peterli@clarunis.ch, geoPoint lat: 47.55839, lon: 7.57327, locations facility: Hôpitaux universitaires de Genève, city: Geneva, country: Switzerland, contacts name: Minoa Jung, PD Dr. med., role: CONTACT, email: minoa.jung@hcuge.ch, geoPoint lat: 46.20222, lon: 6.14569, locations facility: Nuffield Health Bristol Hospital, city: Bristol, country: United Kingdom, contacts name: Dimitri Pournaras, PhD, role: CONTACT, email: dpournaras@doctors.org.uk, geoPoint lat: 51.45523, lon: -2.59665, locations facility: King's College Hospital, city: London, country: United Kingdom, contacts name: Francesco Rubino, MD, role: CONTACT, email: francesco.rubino@kcl.ac.uk, geoPoint lat: 51.50853, lon: -0.12574, locations facility: Queen Mary University, city: London, country: United Kingdom, contacts name: William Alazawi, MB BChir PhD, role: CONTACT, email: w.alazawi@qmul.ac.uk, geoPoint lat: 51.50853, lon: -0.12574, hasResults: False