Clinical trial NCT02526732: Hepatic Inflammation and Physical Performance in Patients With NASH
Official title: Influence of Hepatic Inflammation and Hepatocellular Apoptosis on Physical Performance and Training Effect in Patients With Non - Alcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: NASH
fatty Liver
VO2 max
M30 antigen
Lead sponsor: Johannes Gutenberg University Mainz
Sponsor class: OTHER
First posted: 2015-08-18
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The aim of the study is to examine the influence of hepatic inflammation or damage on physical performance (maximal oxygen uptake, VO2max) depending on the histologic state of the liver. The study population are patients with fatty liver disease and non-alcoholic steatohepatitis (NASH). All study participants obtain an individual training plan with individual and group training sessions for a period of 8 weeks. At the beginning and end of the training phase a sport physiological examination is carried out. In the study group the effect of regular examinations is surveyed by surrogate parameters of liver inflammation.

Detailed description: The study is planned over a period of 24 months. Study participants should be twice examined sport physiologically in a period of 12 weeks. In the study group the influence of regular exercise on surrogate parameters of liver inflammation is investigated over a study period of 8 weeks. Before the exercise all study participants are subjected to a first physiological examination (about 3 hours). This includes a physical examination with detection of body weight, waist circumference and body fat analysis, venous blood, oral glucose tolerance test, ultrasonography of the liver and determination of endothelial function (flow-mediated vasodilatation, FMD) by Doppler analysis. Within 4 weeks after the first examination a sport physical examination is carried out at the Institute of Sports Science at the University of Mainz. This examination contains identification of physical fitness and individual lactate performance diagnostics. In addition, indirect calorimetry is carried out under exercise conditions using spiroergometry to determine the maximal oxygen uptake (VO2max) with special emphasis on the fat metabolism rate at low physical activity. Subsequently to the examination an 8-week training period based on individual training / performance plans is followed. The training plans include independently running exercises for 30-45 minutes two to three times a week. Every two weeks group training sessions are offered accompanied by a sports physician. Within the planed four groups training sessions blood samples will be taken to determinate free circulating DNA and assess lactate values under exercise conditions. After the training phase, a second sport physical examination including physical performance and a final physiological examination including surrogate parameters of liver inflammation are carried out. For statistical analysis, the physical performance of the study participants is examined. Hence patients with histologically proven NASH (NAS score) and confirmed inflammation (increased M30 antigen) are compared to age and gender matched patients with histologically proven fatty liver without inflammation reaction as well as to retrospective data of healthy subjects.

Eligibility criteria: Inclusion Criteria:

* histologically proven NASH or fatty liver disease

Exclusion Criteria:

* bariatric surgery within the last 5 years
* BMI\< 18,5 kg/m2 or \> 45 kg/m2
* heart attack or stroke within the last 6 months
* higher-grade coronary artery disease (CAD III-IV)
* chronic obstructive pulmonary disease (asthma , COPD)
* renal insufficiency
* uncontrolled hypertension or metabolic abnormalities
* alcohol consumption \> 30 g / day (male) and \> 20 g / day (female)
* pregnancy
* concomitant medication able to cause a secondary NASH (eg tamoxifen , corticosteroids )
* concomitant medication able to affect inflammation (eg TNF antagonists)
* concomitant anticoagulant medication (eg phenprocoumon, NOAC)
* other immunological or inflammatory diseases (eg, systemic lupus erythematosus)
* musculoskeletal disorders, preventing sport physiological investigations

Primary outcomes:
measure: Change in physical performance
timeFrame: 0-8 weeks
Secondary outcomes:
measure: Change in liver inflammation
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: University Medical Center of the Johannes Gutenber Univeristy
Study officials:
affiliation: I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz
name: Peter R Galle, MD
role: STUDY_DIRECTOR
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