Impact of Fructose Consumption on Intestinal Permeability in Non-alcoholic Fatty Liver Disease (NAFLD) - a Pilot Study.

NCT01696487 | Completed DMC

• 1 other identifier: Fru1.0
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The spectrum of NAFLD as emerging epidemic ranges from steatosis to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Disease progression is poorly understood and treatment options are limited. Fructose overconsumption has been associated with gut permeability and progression of NAFLD. To unravel the mechanisms of fructose-induced intestinal changes, volunteers will receive a 4-week fructose challenge prior to assessment of intestinal permeability/translocation using endomicroscopy, sugar probes, serum markers of intestinal damage, inflammation, iron/copper homeostasis and histological/molecular analysis of intestinal biopsies. Findings in volunteers will be compared with liver patients undergoing study procedures without fructose challenge. Translational in vitro experiments will explore cellular responses to fructose and endotoxin. This project should provide novel insights into dietary induced alterations of the gut integrity in progression of NAFLD to NASH.

Conditions

Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis

Keywords

non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; NAFLD; NASH

Outcome Measures

Primary Outcomes (2)

• Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy

  Gaps per 1000 intestinal cells will be assesed during gastroscopy by confocal laser endomicroscopy at time point 1 in all study groups and after the 4 week fructose challange in healthy volunteers only

  Time point 1 (day 1 - all study groups)

• Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy

  Gaps per 1000 intestinal cells will be assesed during gastroscopy by confocal laser endomicroscopy at time point 1 in all study groups and after the 4 week fructose challange in healthy volunteers only

  point 2 (week4/day28 - after fructose challange; healthy volunteers only)

Study Arms (4)

Healthy Volunteers

EXPERIMENTAL

Volunteers will be challenged with oral 150g Fructose per day for 28 days.

Dietary Supplement: High oral Fructose challenge (150g per day for 28 days)

NAFLD

NO INTERVENTION

Patients with confirmed fatty liver (imaging positive) will be compared at baseline with other arms.

NASH

NO INTERVENTION

Patients with confirmed non-alcoholic steatohepatitis (biopsy proven) will be compared at baseline with other arms.

Hepatitis C genotype 1 (HCV-GT1)

NO INTERVENTION

Patients with confirmed hepatitis C genotype 1 will be compared at baseline with other arms and act as different liver disease control group

Interventions

High oral Fructose challenge (150g per day for 28 days) DIETARY_SUPPLEMENT

Healthy Volunteers

Eligibility Criteria

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

You may not qualify if:

• Pregnancy and lactation
• Imprisoned persons
• Inflammatory bowel conditions (celiac disease, Crohn's disease, ulcerative colitis)
• Prior bariatric surgery
• Alcoholic steatohepatitis and/or alcohol consumption \> 140 gramms per week (or \> 30g/day)
• 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) (except for group (4): defined as HCV, genotype 1)
• Known allergic reaction to the drugs used (see material and methods)
• Intake of drugs known to accumulate intrahepatic lipids (e.g. steroids/glucocorticoids, tamoxifen, amiodarone, perhexiline maleate, synthetic estrogens, antiretroviral agents, tetracycline, minocycline, certain pesticides, methotrexate)
• Intake of drugs known to drive fibrosis/cirrhosis (e.g. azathioprine, oral contraceptive pills)
• Inability or contraindications to perform study procedures
• General and absolute endoscopy contraindications

Sponsors & Collaborators

• Medical University of Vienna: lead
• State Government of Vienna, Austria (Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien): collaborator

Study Sites (1)

Medical University of Vienna, General Hospital of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Michael Trauner, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL 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: September 1, 2012
• First Posted: October 1, 2012
• Study Start: February 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2014
• Last Updated: September 28, 2015

Record last verified: 2015-09

Locations

AU (1)