Effect of DMR in the Treatment of NASH — DMR_NASH_001  

NASH - Nonalcoholic Steatohepatitis Clinical Trial

Official title: Evaluation of Duodenal Mucosal Resurfacing (DMR) for the Treatment of Non Alcoholic Steatohepatitis (NASH), a Proof of Concept Study

Status Completed

Clinical Trial Summary

Non-alcoholic fatty liver disease (NAFLD) is a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. NASH is part of continuum of metabolic syndrome and constitutes a serious public health concern manifesting by premature cardiovascular disease, end stage diabetes complication and will likely become the first cause of end stage liver disease. Insuline resistance is the hallmark of NASH. Some recent studies both in animals and humans have demonstrated abnormal hypertrophy of the duodenal mucosa, changes in enteroendocrine cell density and number, endocrine hyperplasia, and alterations in gut hormone signaling highlighting the role of the upper intestine gut in glucose homeostasis and thus insulin sensitizing. Given these physiological and pathophysiological features, abrasion of duodenal mucosa was assessed both in animals and humans. The investigators reported an improvement in both glucose homeostasis and transaminases levels suggesting possibly an improvement of NASH. Until now, lifestyle medication is the only recognized efficient treatment for fatty liver disease. Unfortunately, only a minority of patients achieve a significant weight loss and lifestyle modifications. The investigators aim to study the duodenal mucosal resurfacing procedure in patients with NASH biopsy proven in a proof of concept study allowing to assess this technique as a potential treatment to NASH.

Clinical Trial Description

Introduction

Non-alcoholic fatty liver disease (NAFLD) is a frequent disease affecting up to 25% of the USA population, 2-44% in Europe and up to 42,6-69,5% in patients with type 2 diabetes. It is a disease that could progress from simple steatosis to non-alcoholic steatohepatitis (NASH), hepatic cirrhosis and hepatocarcinoma. NASH is part of continuum of a metabolic syndrome and constitutes a serious public health concern, manifesting by premature cardiovascular disease, end stage diabetes complication and will likely become the first cause of end stage liver disease.

Insulin resistance is the hallmark of NASH. Some recent studies both in animals and humans have demonstrated abnormal hypertrophy of the duodenal mucosa, changes in enteroendocrine cell density and number, endocrine hyperplasia, and alterations in gut hormone signaling highlighting the role of the upper intestine gut in glucose homeostasis and thus insulin sensitizing.

Given these physiological and pathophysiological features, abrasion of duodenal mucosa was assessed both in animals and humans. The investigators reported an improvement in both glucose homeostasis and transaminases levels suggesting possibly an improvement of NASH.

Until now, lifestyle medication is the only recognized efficient treatment for fatty liver disease. Unfortunately, only a minority of patients achieve a significant weight loss and lifestyle modifications.

The investigators aim to study the duodenal mucosal resurfacing procedure in patients with NASH biopsy proven in a proof of concept study allowing to assess this technique as a potential treatment to NASH.

Design of study The study is designed as a single arm, proof of concept, non-randomized, open label trial to be conducted at one investigational site. All patients with biopsy proven NASH will undergo an upper endoscopy to perform a duodenal mucosal resurfacing procedure. Evolution of liver steatosis (assessed by MRI), insulin resistance (assessed by oral glucose tolerance test), liver damage (evaluated by blood tests), liver elastography (assessed by fibroscan, fibrotest), biometric parameters will be performed pre- and post-procedure.

Primary outcome :

• Feasability and safety of duodenal mucosal resurfacing, using Revita ™ duodenal mucosal resurfacing after submucosal injection, in patients with NASH.

Secondary outcomes:

• Evolution of steatosis assessed by MRI 6 months after the procedure.

• Evolution of liver fibrosis (assessed by Fibroscan, Fibrotest, Fibrosis four score (FIB-4) and NAFLD fibrosis score) at 6 and 12 months after the procedure.

• Evolution of liver tests at 6 and 12 months after the procedure.

• Evolution of insulin resistance at 1,3,6 and 12 months after the procedure. ;

Related Conditions & MeSH terms

• Fatty Liver
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease

• NCT number: NCT03536650
• Study type: Interventional
• Source: Erasme University Hospital
• Status: Completed
• Phase: N/A
• Start date: November 8, 2017
• Completion date: December 31, 2020