Effect of High Intensity Exercise Rehabilitation on Liver Function and Insulin Sensitivity in Patients With MASLD
- Conditions
- Exercise TherapyMetabolic Dysfunction-associated Steatotic Liver Disease
- Interventions
- Other: Combined aerobic + strength trainingOther: Combined strength + HIIT training
- Registration Number
- NCT06359444
- Lead Sponsor
- University Ghent
- Brief Summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, and is associated with obesity and the metabolic syndrome. Physical activity and lifestyle interventions are among the most recommended treatments for individuals with MASLD.
In this RCT, we will evaluate the effect of combined exercise training "strength and aerobic training" versus "strength and high intensity training (HIIT)". The main outcome parameter is the severity of liver steatosis. Patients will be recruited at the fatty liver clinic of the UZ Gent.
- Detailed Description
Physical activity and lifestyle interventions, including exercise, are recommended for individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). Weight loss has been found to improve MASLD histologically, but exercise alone can also reduce liver fat accumulation, even without significant weight loss. Exercise has positive effects on chronic inflammation, type 2 diabetes mellitus (T2DM), and mitochondrial function in MASLD patients. Studies suggest that both aerobic and resistance exercise are effective in reducing fat content and liver enzyme levels in MASLD, and thereby generate positive effects on insulin sensitivity and cardiovascular risk. The potential of high-intensity interval training (HIIT) is large in various settings, but was never explored in this population. Moreover, the combination with strength training can have additional health effects which remain to be explored.
All subjects are recruited in the liver steatosis outpatient clinic of the university hospital in Ghent by the physicians and researchers of this study. After patient selection and obtaining informed consent, they will be screened in the rehabilitation center for cardiorespiratory fitness.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 92
- Diagnosed with MASLD by ultrasound, CAP and/or biopsy
- Age between 18 and 75 years old
- No significant liver fibrosis (Fibroscan < 7.5 kPa; if it is between >7.5 and <10, there must be absence of liver fibrosis in the biopsy)
- Presence of other liver diseases that may contribute to the clinical presentation in the patient
- Severe cardiovascular, orthopedic, physical or other illnesses that make it impossible to participate in the study's exercise rehabilitation program or where safety cannot be guaranteed
- Pregnancy
- Pharmacological treatment that directly affects MASLD (e.g. GLP-1 analogues)
- A change in medication in the last three months before the study that affects metabolic disease stability
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combined strength + aerobic training Combined aerobic + strength training The patients in this group will exercise for 14 weeks. It is a combination of strength and aerobic exercise. Combined strength + HIIT Combined strength + HIIT training The patients in this group will exercise for 14 weeks. The first 6 weeks consists of combined aerobic and strength exercise, following the protocol from the active comparator group. They will switch to combined strength and HIIT exercise for the remaining 8 weeks.
- Primary Outcome Measures
Name Time Method Liver steatosis by CAP before training and after training (14 weeks) Liver stiffness measurement will be performed using vibration-controlled transient elastography, more specifically the Fibroscan. This method measures the fat accumulation in the liver (dB/m) and the level of scar tissue (kPa), represented as the CAP or steatosis score and the fibrosis score respectively.
Liver steatosis on ultrasound before training and after training (14 weeks) Ultrasound can demonstrate hepatic fatty tissue, estimating severity based on liver-kidney contrast, resolution loss thv the intrahepatic blood vessels, and visibility of the diaphragm. On this basis, a score 0-3 can be assigned.
- Secondary Outcome Measures
Name Time Method Strength before training and after training (14 weeks) Strength will be measured by 1RM determination of the muscle groups that will be trained (leg press, adductors, vertical traction, chest press, abdominal and back muscles). This measurement will be performed at baseline, after 10 weeks and at the end of the study
Cardiovascular function before training and after training (14 weeks) Blood pressure measurements:
Before and after exercise, systole and diastole blood pressure will be measured. Blood pressure will be measured three times and the average value recorded.waist before training and after training (14 weeks) Waist circumference is measured in standing position with a measuring tape just above the iliac crest, to the nearest 0.1 centimeter (cm).
TNF-alfa before training and after training (14 weeks) TNF-α is a pro-inflammatory cytokine produced by macrophages and will be measured in blood. Inflammation in NAFLD causes TNF-α to be released into the body. The amount is increased in patients with NAFLD and correlates with the level of fat mass and insulin resistance.
Hepatokines before training and after training (14 weeks) Hepatokines will be measured in blood. These are proteins secreted by the liver which have a demonstrated association with metabolic function/dysfunction. These include fetuin-A, FGF-21, follistatin etc.
Maximal exercise test before training and after training (14 weeks) A ramp protocol will be performed starting at 25 watts, adding 25 watts per minute each time.
This test will be administered using ergospirometry to derive measures for aerobic physical condition.Interleukine before training and after training (14 weeks) IL-6 and IL-8 serum levels will be measured in blood. These are correlate with the progression of liver fibrosis and are elevated in patients with chronic liver disease.
Adipokines before training and after training (14 weeks) Adipokines will be measured in blood. These are proteins secreted by the adipose tissue which have a demonstrated association with metabolic function/dysfunction. These include leptin, adiponectin, etc.
BMI before training and after training (14 weeks) BMI will be calculated.
BIA before training and after training (14 weeks) Bioelectrical impedance analysis (BIA) will be performed to determine lean mass and fat percentage.
SF-36 before training and after training (14 weeks) Quality of life will be measured using SF-36 (a standard questionnaire).
Insulin sensitivity before training and after training (14 weeks) Insulin sensitivity will be assessed by calculation of the HOMA-IR index (fasting glucose x insulin)
Myokines before training and after training (14 weeks) Myokines will be measured in blood. These are proteins secreted by the muscle which have a demonstrated association with metabolic function/dysfunction. These include myostatin, brain-derived neurotrophic factor, etc....
Liver transaminases before training and after training (14 weeks) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are enzymes located primarily in liver cells. An elevation of these enzymes in the bloodstream may indicate liver damage or inflammation.
Weight before training and after training (14 weeks) Weight will be measured using a scale to the nearest 0.1 kilogram (kg).
Heigth before training and after training (14 weeks) Height will be measured to the nearest 0.1 meter (m) with a stadiometer.
Trial Locations
- Locations (1)
Ghent University Hospital
🇧🇪Ghent, Belgium