Exercise Study in Subjects With NAFLD

Study Overview
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Brief Summary
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Non-Alcoholic Fatty Liver Disease is the most common cause of chronic liver diseases. The benign non-alcoholic fatty liver, characterized by excessive fat accumulation, can evolve into non-alcoholic steatohepatitis and liver cancer. The recommendation nowadays is a lifestyle change with physical exercise and diet to reduce liver fat and improve inflammation. Besides this, a leaky gut and dysbiosis have an impact on the liver, and exercise ameliorates the diversity of gut microbiota and permeability of the intestine. The aim of this study is to find out a link between exercise and the gut-liver axis regarding the stage of liver adiposity and define exercise-responsive gut microbiome in NAFLD patients

Detailed Description
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For this 12-week randomised controlled intervention 60 subjects between 18 and 70 years old, diagnosed with NAFLD and body mass index under 35 kg/m2 will be recruited. They will be randomly assigned in a high-intensity aerobic interval training (n=30) and a control group with a sedentary lifestyle (n=30). The intervention group follows a supervised high-intensity aerobic interval training two times per week and additionally, an individualised home workout program to have 3 hours of aerobic training per week. Blood samples, adipose tissue biopsy, 24h-urine and faecal samples will be collected at the baseline, midway (only stool) and at the end of the study. Dietary intake will be analysed at weeks 0, 6, 12.

Official Title
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A Randomised Controlled Exercise Intervention in Subjects With Non-alcoholic Fatty Liver Disease

Conditions
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Non-Alcoholic Fatty Liver Disease, Gastrointestinal Microbiome, Exercise

Intervention / Treatment
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* Behavioral: high-intensity aerobic interval training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed NAFLD BMI:25 - 35 kg/m^2 Exclusion Criteria: acute illness or current evidence of acute or chronic inflammatory or infective diseases liver disease (e.g. Wilsons disease/alpha-1-antitrypsin deficiency, Hepatitis B and C, hemochromatosis) bleeding disorder, anticoagulation medication subjects with diagnosed type 1 diabetes or diagnosed type 2 diabetes with insulin or Glucagon-like peptide-1 agonist treatment diagnosed depression and mental illness any condition preventing physical activity smokers alcohol abuse (daily consumption ≥ 30 g for men and ≥ 20 g for women)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study contains two arms. One arm is the control group without any changes in their lifestyle (sedentary lifestyle) and the other arm is the intervention group with a high-intensity interval training. Both groups have no changes in their diets.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control-group<br>Subjects diagnosed with NAFLD and a sedentary lifestyle will have no changes in their habits and diets. | |
| Experimental: Exercise-group<br>This group with diagnosed NAFLD patients will perform a high-intensity aerobic interval exercise training without changing their diets. | Behavioral: high-intensity aerobic interval training<br>* The intervention group will follow a high-intensity interval training protocol on a cycle ergometer for 2 times per week and 1 time an individualised home workout program to have a total exercise amount of 3 hours. Leisure time physical activity at baseline as well as during the intervention period will be assessed by Polar Active devices.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in liver fat content | Changes in liver fat content by means of magnetic resonance imaging (MRI) /magnetic resonance spectroscopy (MRS) | 12 weeks (baseline and endpoint) | 
| Gut microbiota changes | Changes in the composition and richness of gut microbiota through metagenomic analyses | 12 weeks (baseline and endpoint) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in glucose profile | Using Freestyle Libre for 2 weeks before the beginning of the intervention and during the last 2 weeks of the intervention to measure tissue glucose concentrations throughout the day | 14 weeks (two weeks preceding the intervention and during the last weeks of the intervention) | 
| Changes in protein expression in adipose tissue | To define differences in lipid and glucose metabolism related enzymes, transporters | 12 weeks (baseline and endpoint) | 
| Changes in low-grade inflammation | Cytokine levels (IL1-RA, TNFα, IL-6, MCP-1, IL-1β, TGF-β, IFN-γ, IL-10) in the blood will be measured by ELISA | 12 weeks (baseline and endpoint) | 
| The effect on body composition | Body composition will be measured by bioimpedance | 12 weeks (baseline and endpoint) | 
| Changes in metabolomics | Metabolomics (small molecule intermediates and products of metabolism) in stool, blood and urine will be measured by Liquid chromatography-mass spectrometry (LC-MS) | 12 weeks (baseline and endpoint) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAFLD, Gut microbiota, high-intensity training