Fatty Liver, Nonalcoholic, Non-alcoholic Fatty Liver Disease
Conditions
Keywords
Histologically confirmed NASH, Hepatocyte Injury determined by M30 antigen
Brief summary
The main aim of the study is to determine if an oral supplementation of the LCS has a beneficial effect by itself or even enhances the beneficial effects of a moderate life-style intervention on the progression of NAFLD in humans.
Interventions
BEHAVIORALNutritional Counseling
Nutritional counseling by a trained nutritionist for 12 weeks.
DIETARY_SUPPLEMENTLactobacillus casei shirota (LCS)
The dietary supplement LCS (Yakult plus) will be given 2 times a day for 12 weeks in addition to dietary counseling every 3 weeks.
OTHERNutritional Counseling and LCS
Nutritional counseling by a trained nutritionist in addition to the dietary supplement LCS (2 times a day) for 12 weeks.
Sponsors
University of Jena
Johannes Gutenberg University Mainz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
\- Elevated M30 antigen levels (cutoff: \>200 - 800 U/L) at screening AND hepatic steatosis on ultrasound OR histologically confirmed NASH \- Age 18 to 75 years
Exclusion criteria
* Alcohol intake of more than 30 g/d (men) or 20 g/d (women) * Treatment with ursodeoxycholic acid (UDCA), Vitamin E or other investigational NASH drugs 3 months prior to randomization * Treatment with medications or substances that may induce secondary NASH (e.g., tamoxifen, corticosteroids, amiodarone, methotrexate) or ameliorate NASH (TNF-antagonists) * Treatment with phenprocoumon or warfarin * Hepatocellular carcinoma or non-hepatic malignancy * Decompensated cirrhosis (Child B,C) or a history of decompensation * Liver disease unrelated to NASH, including chronic viral hepatitis B/D or C, autoimmune hepatitis, Wilson's disease or clinical manifest iron overload * Bariatric surgery within the last 5 years * BMI \<18,5 kg/m2 or BMI \>45 kg/m2 * Liver transplantation * Heart failure (New York Heart Association Class II - IV) * Myocardial infarction, instable coronary artery disease , coronary artery intervention or stroke in the previous 6 months * Instable chronic obstructive pulmonary disease, chronic inflammatory bowel disease or rheumatoid arthritis. * Instable renal insufficiency (changes in serum creatinin \> 50% in the last 3 month) or terminal renal insufficiency requiring dialysis * Uncontrolled hypertension (blood pressure \> 180/90 despite therapy) * Uncontrolled diabetes mellitus defined by hemoglobin A1c \> 9 * Food allergies requiring strictly dietary adherence * Pregnant or nursing women * Chronic pancreatitis or history of recurring acute pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of the M30 antigen in the serum | 12 and 24 weeks | Reduction of the M30 antigen as a validated measure of the degree of hepatocellular inflammation and injury |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in indicators of hepatocellular injury and fibrosis | 12 and 24 weeks | Change in indicators of hepatocellular injury (ALT, gammaGT, M30/M60 antigen ratio, ELF score), proinflammatory cytokines (hsCRP, ferritin, plasminogen activator-1, endotoxin), surrogate parameters of liver fibrosis (fibrosis marker panels, Fibrotest, ELF score) and relative liver stiffness (assessed by Fibro Scan) |
| Change in metabolic risk factors | 12 and 24 weeks | Changes in metabolic risk factors (BMI, waist circumference, Homeostasis Model Assessment/Matsuda Score, serum lipids), changes in oral glucose tolerance and changes in hepatic steatosis will be assessed. |
| Saftey and tolerability | 12 and 24 weeks | Safety is assessed by (1) clinical examination, (2) clinical chemistries including serum electrolytes, renal, liver function tests and markers of pancreatic injury. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Improvement in measures of nutritional physiology | 12 and 24 weeks | Improvement of nutritional physiology, compliance, self-perceived efficacy, emotional eating behavior using a validated questionnaires. |
Countries
Germany
Outcome results
None listed