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…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the reduction of liver fat levels and
other markers of NAFLD after 12 weeks of morning or evening exercise.
Secondary outcome
Secondary endpoints include the improvement of insulin resistance, circulating
levels of liver enzymes, fitness, and gut microbiota composition in response to
morning or evening exercise.
Background summary
Non-alcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing
prevalence that can progress from simple steatosis to non-alcoholic
steatohepatitis (NASH) with hepatic fibrosis and, ultimately, to cirrhosis and
hepatocellular carcinoma (HCC). Not only increases NAFLD liver-related
morbidity and mortality, patients with NAFLD are at high risk for developing
type 2 diabetes (T2DM) and cardiovascular diseases. Since NAFLD is mainly
associated with obesity and increasingly common as a result of the *Western
lifestyle* (i.e. high-caloric diet, physical inactivity and poor physical
fitness), the cornerstone of the treatment of NAFLD consists of lifestyle
adjustments such as exercise training. Many of the processes that are
dysregulated in NAFLD and modulated by exercise, including energy metabolism,
whole-body inflammation and the interplay with the gut microbiota, are under
control of the internal circadian clock. However, it is unknown at what time of
day the circadian control aligns best with exercise training and, therefore,
what the *ideal* training time is to maximize the impact on NAFLD.
Study objective
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 the gut microbiota.
Study design
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 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 the steep ramp
test.
Study burden and risks
The research can cause discomfort/adverse effects. Dangerous side effects are
not to be expected. Although the training program is adapted to the physical
capabilities, the participants may initially feel muscle pain after the
training sessions. It is expected that participating in this study will improve
the physical condition of the participants, it is also possible that they will
lose weight and their blood pressure will be lowered, but this is not certain.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
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
- 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
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83431.058.22 |