NASH - Nonalcoholic Steatohepatitis Clinical Trial
Official title:
A Multicenter, Controlled Study to Evaluate the Efficacy and Safety of an Endoscopic Sutured Gastroplasty (With Endomina Device) in Patients With Non Alcoholic Steatohepatitis (NASH) and Fibrosis.
Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver diseases characterized by liver steatosis which can, in a minority of patients, progress to nonalcoholic steatohepatitis (NASH), fibrosis, and ultimately hepatocellular carcinoma and liver failure. NASH is also recognized as an independent cardiovascular risk factor. Currently, weight loss is the only validated treatment for NASH and also positively affect all the features of metabolic syndrome. Considering the known positive metabolic effects of bariatric surgery, efforts have been exerted to develop minimally endoscopic procedures aiming to induce weight loss. Therefore, we would like to evaluate in patients with NASH disease and fibrosis, the impact of an endoscopic sutured gastroplasty (with Endomina® device) on: - Mainly liver histological endpoints but also, - Surrogate markers of hepatic inflammation and fibrosis and - Surrogate markers of insulin resistance as well as fasting lipid and glycemic profiles.
Background and Rationale: Nonalcoholic steatohepatitis (NASH) is a chronic and progressive disease which can evolve to advanced fibrosis, cirrhosis, liver failure or liver cancer and is associated to a higher risk of death related mainly to cardiovascular events. Weight loss affects positively histological and metabolic features of NASH. Similarly, bariatric surgery improves NASH and fibrosis in morbidly obese patients. New medical devices have been developed to perform endoscopic sutured gastroplasty (ESG) in obese patients. Those affected with coexisting NASH might constitute a good indication for such procedure. Objective: To determine whether ESG improves liver histology, defined as resolution of NASH without worsening of fibrosis at 48 weeks (primary outcome) after ESG. Design, setting and participants: The ENDONASH trial is an investigator-initiated, randomized, controlled, European multicenter study with centrally blinded assessment of the primary outcome. Biopsy proven NASH patients will be randomly assigned (1:1) to either ESG associated to lifestyle intervention (LSI) or LSI alone using a computer-generated, centrally administered allocation, stratified by diabetes status, gender and fibrosis stage. Main inclusion criteria are: biopsy-proven NASH (i.e. Nonalcoholic Fatty Liver Disease Score ≥4), fibrosis stage ≥1, BMI between 27-40, controlled type 2 diabetes. Sample size calculation: The study is powered to establish a 50% response rate of NASH resolution without worsening of fibrosis in the ESG group and a 10% response rate in the control group (according to our previous study1 and a study2 which has evaluated the impact of weight loss on NASH). Accepting an alpha risk of 0.05 (bilateral), a beta risk of 0.2 and a loss rate of 20%, a sample size of 100 patients is needed to achieve statistical significance. Analysis will be carried out by intention-to-treat analysis, which includes all patients who will undergo end-of treatment liver biopsy. Procedures: Eligible patients will be allocated to one arm of the study by means of an online platform (ViedocTM). Demographics, anthropometric measurements, medical history, blood samples and transient elastography will be performed at baseline and at different time points after the randomization during the 48 weeks of follow-up. Finally, all patients will undergo an end-of treatment liver biopsy 48 weeks after randomization. Conclusion: The expected conclusion will allow to demonstrate if ESG, as an add on to LSI, may increases the number of patients with resolution of NASH without worsening of fibrosis at one year. ;
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