Non-Alcoholic Fatty Liver Disease
Conditions
Keywords
Exercise, Circadian rhythms
Brief summary
The goal of this clinical trial is to investigate the different effect of morning and evening exercise training in individuals with non-alcoholic fatty liver disease (NAFLD). The main question it aims to answer is: • Is morning or evening exercise better for the treatment of NAFLD? Participants will follow a supervised exercise training program for three months with either morning or evening training and the effect on liver health will be assessed. Researchers will compare the morning to the evening exercise group to see if one training timepoint is more effective than the other in reducing the amount of fat in the liver and improving liver health.
Detailed description
The aim of the study is to identify the effect of exercise timing on NAFLD. Additionally, we aim to increase the understanding of the exercise-related modulation of the metabolic and inflammatory processes causing NAFLD, including insulin resistance and dysbiosis of the gut microbiota. Forty obese patients with NAFLD will be enrolled by randomization to participate in an exercise training program over 12 weeks, either in the morning (n=20) or evening (n=20). Blood and stool samples will be collected before, during and after the intervention to monitor diagnostic markers such as liver enzymes (AST, ALT, GGT, etc.) and changes of the gut microbiota with exercise, respectively. Moreover, mixed meal tolerance tests will be performed before and after the intervention to monitor insulin sensitivity and hepatic fat content and cardiovascular parameters (e.g. arterial stiffness) will be monitored via MRI. Throughout the study, physical fitness will be assessed and monitored using steep ramp tests. Patients will be randomized for a supervised, standardized 50 min morning or evening training, with both progressive endurance and strength elements, in a frequency of 3 times a week for 12 weeks.
Interventions
BEHAVIORALExercise training
Mixed exercise training containing strength and endurance elements carried out under supervision
Sponsors
Maag Lever Darm Stichting
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 45 years and ≤ 75 * Obese (BMI \> 27 kg/m2) * Males and postmenopausal females * Caucasian * Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound, CAP score on Fibroscan \> 280, and/or histological signs of steatosis * Sedentary lifestyle (maximum of 20 minutes of moderate-to-vigorous physical activity per day on less than three days per week) * Written informed consent
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liver fat content | 12 weeks | Liver fat content (in %) will be measured by MRI LiverMultiScan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body mass index (BMI) | 12 weeks | Body weight (in kg) and height (in m) will be combined to report BMI in kg/m\^2 |
| Fecal microbiota | 12 weeks | Fecal microbiota composition assessed via microbial sequencing |
| Cardiorespiratory fitness | 12 weeks | Peak workload (Wpeak) will be assessed with a the Steep Ramp Test (SRT) on a cycle ergometer |
| Waist circumference | 12 weeks | Waist circumference (in cm) will be measured with a measuring tape |
| Blood pressure | 12 weeks | Blood pressure (mmHg) will be measured using an arm cuff |
| Plasma levels of liver enzymes | 12 weeks | Plasma levels of aspartate transaminase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) (all in units/L) and bilirubin (in umol/L) will be quantified in the laboratory |
| Hepatic fibrosis | 12 weeks | Hepatic stiffness (in kPa) will be measured as a proxy for liver fibrosis by Fibroscan (transient elastography) |
| Plasma glucose levels | 12 weeks | Plasma glucose (in mmol/L) will be measured during a mixed meal test after 0, 10, 20, 30, 40, 60, 90, 120 and 180 minutes of the ingestion of a mixed meal |
| Blood lipid levels | 12 weeks | Blood triglyceride, LDL-cholesterol and HDL-cholesterol levels (all in mmol/L) will be quantified in the laboratory |
| Physical activity | 12 weeks | Self-reported physical activity (minutes of moderate-intensity activity per week) will be assessed with the International Physical Activity Questionnaire (IPAQ) |
| Sleep | 12 weeks | Sleeping habits (bedtime, time of falling asleep, time of waking up, sleep duration) will be assessed via the Munich Chronotype Questionnaire (MCTQs 5.0). |
| Food intake | 12 weeks | Self-reported food intake (type of food, quantity, time of intake) will be assessed with 3-day food diaries |
| Plasma insulin levels | 12 weeks | Plasma insulin (in pmol/L) will be measured during a mixed meal test after 0, 10, 20, 30, 40, 60, 90, 120 and 180 minutes of the ingestion of a mixed meal |
Countries
Netherlands
Contacts
Primary ContactMilena Schönke, PhD
Backup ContactMaarten E Tushuizen, MD PhD
Outcome results
None listed