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

Study Overview
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Brief Summary
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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.

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

Conditions
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Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers<br>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)<br> <br> |
| No Intervention: NAFLD<br>Patients with confirmed fatty liver (imaging positive) will be compared at baseline with other arms. | |
| No Intervention: NASH<br>Patients with confirmed non-alcoholic steatohepatitis (biopsy proven) will be compared at baseline with other arms. | |
| No Intervention: Hepatitis C genotype 1 (HCV-GT1)<br>Patients with confirmed hepatitis C genotype 1 will be compared at baseline with other arms and act as different liver disease control group | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, NAFLD, NASH