Back to results

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

Primary Purpose

Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis

Status

Completed

Phase

Not Applicable

Locations

Austria

Study Type

Interventional

Intervention

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

About this trial

This is an interventional prevention trial for Non-alcoholic Fatty Liver Disease focused on measuring non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, NAFLD, NASH

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Healthy men and women from 18 to 85, no disease history, no intake of regular medication.
Patients with confirmed (at least one imaging positive) intrahepatic fat accumulation (NAFL), male and female
Patients with confirmed NASH (biopsy within 6 months prior to study), male and female
Diagnosed HCV, genotype 1, male and female

Signed informed consent

General exclusion criteria (for all groups)

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

Sites / Locations

Medical University of Vienna, General Hospital of Vienna

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Arm Label

Healthy Volunteers

NAFLD

NASH

Hepatitis C genotype 1 (HCV-GT1)

Arm Description

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

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

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

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

Outcomes

Primary Outcome Measures

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

Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy

Secondary Outcome Measures

Full Information

NCT ID

NCT01696487

First Posted

September 1, 2012

Last Updated

September 24, 2015

Sponsor

Medical University of Vienna

Collaborators

State Government of Vienna, Austria (Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien)

1. Study Identification

Unique Protocol Identification Number

NCT01696487

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

February 2012 (undefined)

Primary Completion Date

February 2013 (Actual)

Study Completion Date

February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Medical University of Vienna

Collaborators

State Government of Vienna, Austria (Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters der Bundeshauptstadt Wien)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Healthy Volunteers

Arm Type

Experimental

Arm Description

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

Arm Title

NAFLD

Arm Type

No Intervention

Arm Description

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

Arm Title

NASH

Arm Type

No Intervention

Arm Description

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

Arm Title

Hepatitis C genotype 1 (HCV-GT1)

Arm Type

No Intervention

Arm Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

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

Primary Outcome Measure Information:

Title

Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy

Description

Time Frame

Time point 1 (day 1 - all study groups)

Title

Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Healthy men and women from 18 to 85, no disease history, no intake of regular medication. Patients with confirmed (at least one imaging positive) intrahepatic fat accumulation (NAFL), male and female Patients with confirmed NASH (biopsy within 6 months prior to study), male and female Diagnosed HCV, genotype 1, male and female Signed informed consent General exclusion criteria (for all groups) 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Trauner, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of Vienna, General Hospital of Vienna

City

Vienna

ZIP/Postal Code

1090

Country

Austria

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs