The Clock Thickens: Morning or Evening Training for the Treatment of NAFLD?
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Interventions
- Behavioral: Exercise training
- Registration Number
- NCT05987748
- Lead Sponsor
- Leiden University Medical Center
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
- 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 for MRI (claustrophobia, pacemaker, metal implants, etc.)
- Any other liver disease than NAFLD/NASH
- Present excessive alcohol use defined as > 2 units/day
- Recent use (< 3 months) of antibiotics
- Recent changes in dosages of regular medication (< 3 months)
- Recent (< 3 months) weight change (>5%)
- Recent (< 3 months) substantial diet changes
- Cardiovascular co-morbidity defined as heart failure, coronary insufficiency and hypertension in past history
- Comorbidity that contraindicates exercise training and exercise testing or that affects exercise response and exercise capacity
- Ongoing or recent use of glucocorticoids, oral/transdermal hormonal substitution, paclitaxel, theofyllin, amiodarone, myelosuppresive agents
- A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study
- Working night or alternating shifts, known sleeping disorders such as narcolepsy or insomnia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Morning exercise Exercise training Individuals will exercise train at 8 AM three times per week for 12 weeks. Evening exercise Exercise training Individuals will exercise train at 8 PM three times per week for 12 weeks.
- Primary Outcome Measures
Name Time Method Liver fat content 12 weeks Liver fat content (in %) will be measured by MRI LiverMultiScan
- Secondary Outcome Measures
Name Time Method Fecal microbiota 12 weeks Fecal microbiota composition assessed via microbial sequencing
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
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
Hepatic fibrosis 12 weeks Hepatic stiffness (in kPa) will be measured as a proxy for liver fibrosis by Fibroscan (transient elastography)
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
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)
Food intake 12 weeks Self-reported food intake (type of food, quantity, time of intake) will be assessed with 3-day food diaries
Waist circumference 12 weeks Waist circumference (in cm) will be measured with a measuring tape
Body mass index (BMI) 12 weeks Body weight (in kg) and height (in m) will be combined to report BMI in kg/m\^2
Cardiorespiratory fitness 12 weeks Peak workload (Wpeak) will be assessed with a the Steep Ramp Test (SRT) on a cycle ergometer
Blood pressure 12 weeks Blood pressure (mmHg) will be measured using an arm cuff
Blood lipid levels 12 weeks Blood triglyceride, LDL-cholesterol and HDL-cholesterol levels (all in mmol/L) will be quantified in the laboratory
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).
Trial Locations
- Locations (1)
Leiden University Medical Center
🇳🇱Leiden, South Holland, Netherlands