Nutritional Counseling vs. Nutritional Supplements for NASH - a Randomized Prospective, Open Label Pilot Study

Study Overview
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Brief Summary
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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.

Official Title
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Nutritional Counseling Versus Nutritional Supplements for the Treatment of NASH - a Randomized Prospective, Open Label Pilot Study (Nuces NASH)

Conditions
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Non-alcoholic Fatty Liver Disease, Fatty Liver, Nonalcoholic

Intervention / Treatment
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* Behavioral: Nutritional Counseling
* Dietary Supplement: Lactobacillus casei shirota (LCS)
* Other: Nutritional Counseling and LCS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nutritional Counseling<br>The nutritional counseling group will receive dietary counseling focusing on a reduction of fructose intake by a trained nutritionist for 12 weeks every 3 weeks. | Behavioral: Nutritional Counseling<br>* Nutritional counseling by a trained nutritionist for 12 weeks.<br>|
| Experimental: Nutritional Counseling and LCS<br>The dietary supplement LCS (Lactobacillus casei shirota ) will be given 2 times a day for 12 weeks in addition to the nutritional counseling every 3 weeks. | Other: Nutritional Counseling and LCS<br>* Nutritional counseling by a trained nutritionist in addition to the dietary supplement LCS (2 times a day) for 12 weeks.<br>* Other names: Nutritional Counseling and Yakult plus;|
| Experimental: Lactobacillus Casei Shirota<br>The dietary supplement LCS (Lactobacillus casei shirota ) will be given 2 times a day for 12 weeks. | Dietary Supplement: Lactobacillus casei shirota (LCS)<br>* The dietary supplement LCS (Yakult plus) will be given 2 times a day for 12 weeks in addition to dietary counseling every 3 weeks.<br>* Other names: Yakult plus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of the M30 antigen in the serum | Reduction of the M30 antigen as a validated measure of the degree of hepatocellular inflammation and injury | 12 and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in indicators of hepatocellular injury and fibrosis | 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) | 12 and 24 weeks | 
| Change in metabolic risk factors | 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. | 12 and 24 weeks | 
| Saftey and tolerability | Safety is assessed by (1) clinical examination, (2) clinical chemistries including serum electrolytes, renal, liver function tests and markers of pancreatic injury. | 12 and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Histologically confirmed NASH, Hepatocyte Injury determined by M30 antigen