Unravelling Mechanisms of Fructose vs Glucose Consumption in the Pathogenesis and Progression of NAFLD

NCT02075164 | Unknown DMC

• 1 other identifier: Fru2.0
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum ranging from simple fatty liver over steatohepatitis (NASH) to liver cirrhosis and cancer (HCC) and is a major and increasing health problem affecting nearly 40% of the general population. Moreover, NAFLD is an important risk factor for progression of diabetes and atherosclerosis. However, the pathomechanisms determining disease progression are poorly understood. The overall aim of this project is to test the central hypothesis that excessive fructose consumption provides a multiple metabolic hit in the pathogenesis and progression of NAFLD/NASH by impairment of hepatic lipid homeostasis and mitochondrial function resulting in hepatic lipotoxicity with inflammasome activation and disturbed interorgan cross-talk among insulin sensitive tissues.

Conditions

Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis

Keywords

Non-alcoholic Fatty Liver Disease; Non-alcoholic steatohepatitis; NAFLD; NASH

Outcome Measures

Primary Outcomes (1)

• Intrahepatic total fat and ipid composition assessed by Magnetic resonance spectroscopy

  At baseline and on the last day of the study (day 56) Magnetic resonance spectroscopy will be carried out in healthy volunteers. (Prior and after double-blinded fructose versus glucose consumption for 8 weeks in each healthy volunteer). In NAFLD and NASH patients Magnetic resonance spectroscopy will only be carried out at baseline, as this arms/groups do not undergo an oral fructose/glucose challenge. Baseline measures between healthy volunteers and NAFLD/NASH groups/arms will be compared to assess differences between healthy individuals and patients. Baseline and day 56 measures in healthy volunteers after fructose/glucose consumption will be compared to assess the influence of the dietary challenge.

  Healthy volunteers: Baseline, day 56 (8 weeks); NAFLD/NASH patients: Baseline

Study Arms (4)

Fructose

EXPERIMENTAL

Volunteers will be challenged with oral 150g Fructose per day for 56 days.

Dietary Supplement: Fructose; Dietary Supplement: Glucose

Glucose

EXPERIMENTAL

Volunteers will be challenged with oral 167g Fructose per day for 56 days.

Dietary Supplement: Fructose; Dietary Supplement: Glucose

NAFLD

NO INTERVENTION

Patients with confirmed simple fatty liver will be compared at baseline with other arms.

NASH

NO INTERVENTION

Patients with confirmed non-alcoholic steatohepatitis will be compared at baseline with other arms.

Interventions

Fructose DIETARY_SUPPLEMENT

High oral Fructose challenge (150g per day for 56 days)

Fructose; Glucose

Glucose DIETARY_SUPPLEMENT

Dietary Supplement: High oral Fructose challenge (167g per day for 56 days)

Fructose; Glucose

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• Pregnancy and lactation (blood/urine pregnancy test will be performed for female volunteers at baseline and week 4)
• Imprisoned persons
• Declined informed consent
• Inflammatory bowel conditions (celiac disease, Crohn's disease, ulcerative colitis)
• Prior bariatric surgery
• Alcoholic steatohepatitis and/or alcohol consumption \> 140 grams per week (or \> 30g/day) 45
• Other liver diseases (autoimmune, genetic, cholestatic, Wilson disease, Weber-Christian disease, partial lipodystrophy of the face sparing type, abetalipoproteinemia, and jejunal diverticulosis with bacterial overgrowth).
• Virus hepatitis (A, B, C)
• Known allergic reaction to the drugs used (see material and methods)
• Intake of drugs known to accumulate intrahepatic lipids and significantly interfere with metabolism (e.g. steroids/glucocorticoids, tamoxifen, amiodarone, perhexiline maleate, antiretroviral agents, tetracycline, minocycline, certain pesticides) 45
• Inability or contraindications to perform study procedures
• Fructose malabsorption diagnosed by two consecutive positive fructose hydrogen breath test
• MRI contraindications Study participants with claustrophobia Study participants carrying
• a cardiac pacemaker
• an insulin pump

Sponsors & Collaborators

• Prof. Michael Trauner, MD: lead
• Wiener Wissenschafts-, Forschungs- und Technologiefonds: collaborator

Study Sites (1)

Medical University of Vienna, General Hospital of Vienna Vienna, Vienna, Austria 1090

Vienna, 1090, Austria

RECRUITING

Related Publications (1)

• Smajis S, Gajdosik M, Pfleger L, Traussnigg S, Kienbacher C, Halilbasic E, Ranzenberger-Haider T, Stangl A, Beiglbock H, Wolf P, Lamp T, Hofer A, Gastaldelli A, Barbieri C, Luger A, Trattnig S, Kautzky-Willer A, Krssak M, Trauner M, Krebs M. Metabolic effects of a prolonged, very-high-dose dietary fructose challenge in healthy subjects. Am J Clin Nutr. 2020 Feb 1;111(2):369-377. doi: 10.1093/ajcn/nqz271.

  PMID: 31796953 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Fructose; Glucose

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Michael Trauner, Prof. MD

  Division of Gastroenterology and Hepatology Department of Internal Medicine III Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Trauner, Prof. MD.

CONTACT

+43140400; michael.trauner@meduniwien.ac.at

Michael Krebs, Prof. MD.

CONTACT

+43140400; michael.krebs@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, Head and Chair of the Division of Gastroenterology and Hepatology, Department of Internal Medicine III

Study Record Dates

• First Submitted: February 6, 2014
• First Posted: March 3, 2014
• Study Start: May 1, 2013
• Primary Completion: June 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 7, 2020

Record last verified: 2020-09

Locations

AU (1)