Impact of Fructose Consumption on Intestinal Permeability in Non-alcoholic Fatty Liver Disease (NAFLD) - a Pilot Study.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •(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
研究组 & 干预措施
Healthy Volunteers
Volunteers will be challenged with oral 150g Fructose per day for 28 days.
干预措施: High oral Fructose challenge (150g per day for 28 days) (Dietary Supplement)
NAFLD
Patients with confirmed fatty liver (imaging positive) will be compared at baseline with other arms.
NASH
Patients with confirmed non-alcoholic steatohepatitis (biopsy proven) will be compared at baseline with other arms.
Hepatitis C genotype 1 (HCV-GT1)
Patients with confirmed hepatitis C genotype 1 will be compared at baseline with other arms and act as different liver disease control group
结局指标
主要结局
Gaps per 1000 intestinal epithelial cells assessed by confocal laser endomicroscopy
时间窗: point 2 (week4/day28 - after fructose challange; healthy volunteers only)
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
时间窗: Time point 1 (day 1 - all study groups)
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
次要结局
未报告次要终点
研究者
Prof. Michael Trauner, MD
Professor, MD, Head and Chair of the Division of Gastroenterology and Hepatology, Department of Internal Medicine III
Medical University of Vienna