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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; Fatty Liver, Nonalcoholic
• Intervention / Treatment: Behavioral: Nutritional Counseling; Other: Nutritional Counseling and LCS; Dietary supplement: Lactobacillus casei shirota (LCS)

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Jena, Germany, 07743
    • Institut für Ernährungswissenschaften, University Jena
  • Mainz, Germany, 55131
    • University Medical Center of the Johannes Gutenber Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nutritional Counseling; 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; Nutritional counseling by a trained nutritionist for 12 weeks.
Experimental: Nutritional Counseling and LCS; 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; Nutritional counseling by a trained nutritionist in addition to the dietary supplement LCS (2 times a day) for 12 weeks.; Other Names: Nutritional Counseling and Yakult plus
Experimental: Lactobacillus Casei Shirota; The dietary supplement LCS (Lactobacillus casei shirota ) will be given 2 times a day for 12 weeks.	Dietary supplement: Lactobacillus 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.; Other Names: Yakult plus

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in measures of nutritional physiology	Improvement of nutritional physiology, compliance, self-perceived efficacy, emotional eating behavior using a validated questionnaires.	12 and 24 weeks

Collaborators and Investigators

• Sponsor: Johannes Gutenberg University Mainz
• Collaborators: University of Jena
• Investigators: Principal Investigator: Jörn M Schattenberg, MD, Johannes Gutenberg Universität; Principal Investigator: Ina Bergheim, PhD, Universität Jena

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): May 10, 2017
• Study Completion (Actual): May 10, 2017

Study Registration Dates

• First Submitted: November 1, 2013
• First Submitted That Met QC Criteria: February 11, 2015
• First Posted (Estimate): February 19, 2015

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Histologically confirmed NASH; Hepatocyte Injury determined by M30 antigen
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: NUCES_NASH-JGU; SCHA 1015/5-1 (Other Grant/Funding Number: DFG)