Clinical trial NCT03995056: Exercise Study in Subjects With NAFLD
Official title: A Randomised Controlled Exercise Intervention in Subjects With Non-alcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Gastrointestinal Microbiome
Exercise
Keywords: NAFLD
Gut microbiota
high-intensity training
Lead sponsor: University of Eastern Finland
Sponsor class: OTHER
Collaborators: name: European Commission
name: Leibniz Institute for Natural Product Research and Infection Biology Hans Knöll Institute
name: Afekta
name: Novogene
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Clinical Microbiomics
name: Kuopio Research Institute of Exercise Medicine
name: Kuopio University Hospital
First posted: 2019-06-21
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Changes in liver fat content
timeFrame: 12 weeks (baseline and endpoint)
measure: Gut microbiota changes
timeFrame: 12 weeks (baseline and endpoint)
Secondary outcomes:
measure: Changes in glucose profile
timeFrame: 14 weeks (two weeks preceding the intervention and during the last weeks of the intervention)
measure: Changes in protein expression in adipose tissue
timeFrame: 12 weeks (baseline and endpoint)
measure: Changes in low-grade inflammation
timeFrame: 12 weeks (baseline and endpoint)
measure: The effect on body composition
timeFrame: 12 weeks (baseline and endpoint)
measure: Changes in metabolomics
timeFrame: 12 weeks (baseline and endpoint)
Other outcomes:
Locations:
city: Kuopio
country: Finland
facility: University of Eastern Finland
Study officials:
affiliation: University of Eastern Finland
name: Ursula Schwab, Prof
role: STUDY_DIRECTOR
References:
citation: 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.