Recruitment

Recruitment Status
Recruiting

Inclusion Criterias

Patients with confirmed NASH (biopsy within 6 months prior to study), HbA1c < 6.5, male and female (1:1).
Signed informed consent, willing and able to perform study procedures.
Healthy men and women from 18 to 85, no disease history, no intake of regular medication, drugs, alcohol (alcohol consumption > 140 grams per week (or > 30g/day) 45) or herbals known to affect liver physiology, male and female (1:1), BMI <= 25.
...
Patients with confirmed NASH (biopsy within 6 months prior to study), HbA1c < 6.5, male and female (1:1).
Signed informed consent, willing and able to perform study procedures.
Healthy men and women from 18 to 85, no disease history, no intake of regular medication, drugs, alcohol (alcohol consumption > 140 grams per week (or > 30g/day) 45) or herbals known to affect liver physiology, male and female (1:1), BMI <= 25.
Patients with prior confirmed (biopsy within 6 months prior to study) intrahepatic fat accumulation/simple fatty liver (NAFL), HbA1c < 6.5, male and female (1:1)

Summary

Conditions
  • Non-alcoholic Fatty Liver Disease
  • Non-alcoholic Steatohepatitis
Type
Interventional
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Prevention

Participation Requirements

Age
Between 18 years and 85 years
Gender
Both males and females

Description

To achieve these goals we will address the following specific hypotheses that Fructose-induced changes in lipid composition of hepatocellular stores determine lipotoxicity which may be associated with abnormalities in mitochondrial function, energy homeostasis, inflammasome activation and cellular i...

To achieve these goals we will address the following specific hypotheses that Fructose-induced changes in lipid composition of hepatocellular stores determine lipotoxicity which may be associated with abnormalities in mitochondrial function, energy homeostasis, inflammasome activation and cellular injury in progression to NASH, effects which will be compared to glucose Non-invasive characterization of fructose (compared to glucose)-induced lipotoxic hepatic and extrahepatic metabolic risk profiles (lipid composition and energy metabolism) obtained by magnetic resonance spectroscopy (MRS) will identify patients with NASH Severity of fructose (compared to glucose)-induced lipotoxic lipid and adenosine triphosphate (ATP) derangements (identified by MRS) critically determines the degree of insulin resistance and abnormalities in hepatic glucose and lipid metabolism Compensatory hyperinsulinemia, secondary to skeletal muscle insulin resistance, may be a primary mechanism of hepatic lipotoxicity and progression to NASH Gender differences in the hepatic and systemic metabolic response to fructose are mediated by the impact of female sex hormones and their nuclear receptors on hepatic lipid metabolism, mitochondrial function and inflammasome activation. Age differences in the hepatic and systemic metabolic response to fructose are mediated by the impact of age related alterations on hepatic lipid metabolism and mitochondrial function. These key hypotheses will be addressed by a translational research consortium including hepatologists, radiologists, physicists, endocrinologists and specialist in gender medicine allowing an integrated mechanistic approach to NAFLD. The strength of the current proposal comes directly from bridging basic science and clinical perspectives of different disciplines involved in the management of NAFLD, including cutting edge non-invasive technologies such as high field MRS metabolic profiling ('virtual metabolic liver biopsy') and mechanistic in vitro experiments. This project will provide novel mechanistic insights in the role of fructose as emerging hepatic 'toxin' in the pathogenesis and progression of NASH, as increasing health problem in Western society. Moreover, this study will clarify the impact of sex and gender on fructose-induced alterations in hepatic and systemic metabolism, providing a rational and scientific basis for future dietary interventions and regulatory actions.

Inclusion Criterias

Patients with confirmed NASH (biopsy within 6 months prior to study), HbA1c < 6.5, male and female (1:1).
Signed informed consent, willing and able to perform study procedures.
Healthy men and women from 18 to 85, no disease history, no intake of regular medication, drugs, alcohol (alcohol consumption > 140 grams per week (or > 30g/day) 45) or herbals known to affect liver physiology, male and female (1:1), BMI <= 25.
...
Patients with confirmed NASH (biopsy within 6 months prior to study), HbA1c < 6.5, male and female (1:1).
Signed informed consent, willing and able to perform study procedures.
Healthy men and women from 18 to 85, no disease history, no intake of regular medication, drugs, alcohol (alcohol consumption > 140 grams per week (or > 30g/day) 45) or herbals known to affect liver physiology, male and female (1:1), BMI <= 25.
Patients with prior confirmed (biopsy within 6 months prior to study) intrahepatic fat accumulation/simple fatty liver (NAFL), HbA1c < 6.5, male and female (1:1)

Locations

Vienna, 1090
Vienna, 1090

Tracking Information

NCT #
NCT02075164
Collaborators
Wiener Wissenschafts-, Forschungs- und Technologiefonds
Investigators
  • Principal Investigator: Michael Trauner, Prof. MD Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna
  • Michael Trauner, Prof. MD Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna