Exercise Study in Subjects With NAFLD (BestTreat)

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

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

Study Overview

• Status: Completed
• Conditions: Exercise; Non-Alcoholic Fatty Liver Disease; Gastrointestinal Microbiome
• Intervention / Treatment: Behavioral: high-intensity aerobic interval training

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Kuopio, Finland, 70200§§
    • University of Eastern Finland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control-group; Subjects diagnosed with NAFLD and a sedentary lifestyle will have no changes in their habits and diets.
Experimental: Exercise-group; 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; 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Eastern Finland
• Collaborators: Kuopio University Hospital; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); European Commission; Kuopio Research Institute of Exercise Medicine; Leibniz Institute for Natural Product Research and Infection Biology; Afekta; Novogene; Clinical Microbiomics
• Investigators: Study Director: Ursula Schwab, Prof, University of Eastern Finland

Publications and helpful links

General Publications

• Babu AF, Csader S, Mannisto V, Tauriainen MM, Pentikainen H, Savonen K, Klavus A, Koistinen V, Hanhineva K, Schwab U. Effects of exercise on NAFLD using non-targeted metabolomics in adipose tissue, plasma, urine, and stool. Sci Rep. 2022 Apr 20;12(1):6485. doi: 10.1038/s41598-022-10481-9.

Helpful Links

• European Union Project: "Building a Gut Microbiome Engineering Toolbox for In-Situ Therapeutic Treatments for Non-alcoholic Fatty Liver Disease"

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2019
• Primary Completion (Actual): June 18, 2020
• Study Completion (Actual): June 18, 2020

Study Registration Dates

• First Submitted: June 10, 2019
• First Submitted That Met QC Criteria: June 20, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: NAFLD; Gut microbiota; high-intensity training
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: BestTreat

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No