Effects of Exenatide (Byetta®) on Liver Function in Patients With Nonalcoholic Steatohepatitis (NASH)
Condition: Nonalcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      The primary objective is to test the hypothesis that 24 weeks of treatment with exenatide
      will improve the histological acitvity of NASH (steatosis,necroinflammation, ballooning),
      summarized in the recently introduced NASH-score in patients with normal, impaired or
      diabetic glucose tolerance compared to dietary guidance alone.
    

Detailed description: 
      Non alcoholic steatohepatitis (NASH), a chronic liver disease characterized by insulin
      resistance, accumulation of hepatic fat and hepatocellular necroinflammation, has been
      recognized as a leading cause of (cryptogenic) liver cirrhosis in developed countries. Given
      the rising prevalence of NASH and the associated socio-economic burden associated, novel
      therapeutic options are warranted. The incretin mimetic Exenatide (Byetta®) exhibits strong
      glucoregulatory activities through its multiple biological effects. In addition, exenatide
      treatment has been shown to improve lipid homeostasis and reduce body weight. Since the
      development of NASH has been tightly linked to the presence of obesity, hyperlipidaemia and
      diabetes, this study will examine, whether 24 weeks of treatment with exenatide will also
      result in improvements in liver function in patients with NASH.

      60 patients with histologically proven NASH will be randomized to receive either exenatide (2
      x 5 µg s.c. for 4 weeks, 2 x 10 µg thereafter) or placebo treatment, in a 1:1 ratio. Liver
      biopsies will be performed after 24 weeks of treatment. In addition, a non-invasive
      assessment of hepatic mitochondrial function will be carried-out using a 13C-methionine
      breath test at baseline, and at weeks 12 and 24. Insulin sensitivity and glucose tolerance
      will be assessed by a hyperinsulinaemic-euglycaemic clamp (baseline and week 24) and an oral
      glucose tolerance test (baseline, weeks 12 and 24). Hepatic fat content will be measured by
      magnetic resonance tomography. Liver enzymes will be monitored closely throughout the study
      period.

      These studies will clarify whether exenatide treatment, in addition to its beneficial effects
      on glucose homeostasis and body weight, will also result in improvements of liver function in
      patients with NASH.
    

Intervention name(s): Exenatide
Intervention type(s): Drug
Intervention description(s): Exenatide; 48 weeks 10 microg injection s.c., twice daily, before the morning and evening meal with a four week wash-in phase with 5 microg injection s.c.twice daily
Intervention MeSH terms: Exenatide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: exenatide; hepatic steatosis; insulin resistance; insulin sensitizers; nonalcoholic fatty liver disease; - GLP1-Analog