Patients with morbid obesity (MB) are investigated. MB is very frequently (90%) associated with non-alcoholic fatty liver disease (NAFLD) comprising a spectrum reaching from steatosis (NAFL) over steatohepatitis (NASH) to fibrosis/cirrhosis. MedDRA version: 9.1 Level: LLT Classification code 10029530 Term: Non-alcoholic fatty liver
Conditions
Interventions
Trade Name: Ursofalk
Product Name: Ursofalk
Pharmaceutical Form: Capsule*
INN or Proposed INN: ursodiol
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-
Sponsors
Hanns-Ulrich Marschall
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Morbidly obese (BMI >35 kg/m2) patients of both gender scheduled for bariatric surgery. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any condition that does not allow bariatric surgery, i.e. major cardiovascular, liver or kidney disease, pregnancy, drug abuse. Insulin-dependent or independent diabetes mellitus.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Ursodeoxycholic acid (UDCA) improves clinical and biochemical serum parameters in a variety of cholestatic liver diseases. The efficacy of UDCA treatment in non-alcoholic fatty liver disease (NAFLD) has been debated and the mechanism(s) of action in humans are still not defined. However, UDCA may may improve insulin resistance and steatosis, as previously shown in mice. We aim to determine whether • UDCA (20mg/kg/d) improves insulin resistance in patients with NAFLD • UDCA improves hepatobiliary transporter expression in NAFLD • UDCA alters hepatic and/or white adipose tissue (WAT) lipase activity and fatty acid/triglyceride (FA/TG) content in NAFLD ;Secondary Objective: • Hepatic steatosis results in impaired expression of hepatobiliary ABC transporters and regulatory nuclear receptors contributing to liver damage and impaired bile acid flux/signalling in NAFLD • Hepatic and/or visceral white adipose tissue (WAT) lipase activity determines fatty acid (FA) release/balance from lipid triglyceride (TG) droplets and FA-mediated lipotoxicity in NAFLD; differences in hepatic and/or WAT activity could explain individual susceptibility to pure NAFL versus steatohepatitis (NASH). ;Primary end point(s): 1) Molecular characterization of ABC transporter expression and bile acid synthetic/metabolic enzymes in patients with different degrees of NAFLD (NAFL vs NASH). 2) Molecular expression of fatty acid synthetic/metabolism enzymes, hepatic lipase activity. 3) To study the impact of UDCA on expression and activity of fatty acid synthetic/metabolism enzymes, ABC transporter expression, regulatory nuclear receptor activity (FXR, PXR, CAR) and FGF 19, hepatic lipase activity, insulin resistance (HOMA), hepatic insulin signaling (IRS), ER stress (PERK, XBP-1). | — |
Countries
Sweden
Outcome results
None listed