Effect of DMR in the Treatment of NASH
Condition: NASH - Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): DMR
Intervention type(s): Device
Intervention description(s): Procedure: DMR Procedure The Fractyl DMR procedure using the Revita System utilizes an over the wire endoscopic approach to ablate the duodenum. The procedure may be completed in an endoscopic suite or in an operating room depending on the facilities and support at each investigative site. All subjects are monitored and anesthetized by conscious sedation per each facility's standard protocol. A full DMR procedure is defined as 5 complete ablations or 9 axial centimeters of circumferentially ablated tissue in the duodenum. Subjects who do not receive any ablations during the DMR procedure will be followed for safety through the 4 week visit and then discontinued from the study.
Other Names:
DMR Revita
Other intervention name(s): Revita
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Metabolic diseases