Study to Investigate the Effects of Different Doses of S-adenosyl-L-methionine (SAMe) in Subjects With Nonalcoholic Fatty Liver Disease and Non-treated Matched Healthy Volunteers as Control Group
Condition: Non Alcoholic Fatty Liver Disease
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: SAMe 1000 mg; SAMe 1500 mg; SAMe 2000 mg
Intervention description: 1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner; 1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner; 2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Steatohepatitis

Summary:

      Investigation the Effects of Different Doses of SAMe in Subjects with Nonalcoholic Fatty
      Liver Disease and non-treated matched healthy volunteers as control group
    

Eligibility criteria:

        Inclusion Criteria

          -  Subjects with non-alcoholic steatohepatitis based on histology in medical history
             within the last 3 years

          -  Subjects in a stable metabolic condition since histology for NASH (Non-alcoholic
             Steatohepatitis)

        Exclusion Criteria

          -  Subjects with extrahepatic biliary obstruction

          -  Subjects with primary sclerosing cholangitis (PSC)

          -  Subjects with primary biliary cirrhosis (PBC)

          -  Any form of malignancy within the past 5 years and/or basal cell carcinoma and
             squamous cell carcinoma of the skin within the past two years

          -  History of active substance abuse (oral, inhaled or injected) within one year prior to
             the study

          -  Subjects with renal impairment (creatinine level of >2.0 mg/dL)

          -  Subjects with a known hypersensitivity to the active substance (ademetionine) or
             methionine or to any of the inactive ingredients

          -  Subjects with known genetic defects affecting the methionine cycle and/or causing
             homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase
             deficiency, Vitamin B12 metabolism defect)

          -  Subjects on total parenteral nutrition in the year prior to screening

          -  Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight
             loss surgery)

          -  Extrahepatic cholestasis (proven by ultrasound)

          -  Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >
             5 upper limit of normal (ULN)

          -  Subject with serum total bilirubin (STB) > 5 ULN

          -  Subjects after liver transplantation and subjects on the waiting list for liver
             transplantation

          -  Subjects with any of the following disease in medical history:

          -  Viral hepatitis (serum positive HBcAb (hepatitis B core antibody) or Hepatitis C Virus
             (HCV) ribonucleic acid (RNA)

          -  Evidence of autoimmune liver disease

          -  Wilson's disease

          -  Hemochromatosis

          -  Alpha-1-antitrypsin deficiency

          -  Known positivity for antibody to human immunodeficiency virus (HIV)

          -  Known heart failure of New York heart Association class 3 or 4

          -  Current or history of significant alcohol consumption for a period of more than three
             consecutive months within five years prior to screening (significant alcohol
             consumption is defined as > 3 U (unit)/day for men and > 2 U/day for women, on
             average) or binge drinking or inability to reliably quantify alcohol consumption.

          -  Clinical or histological evidence of cirrhosis F4

          -  Subjects with history of biliary diversion

          -  Subjects with uncontrolled diabetes mellitus defined by HbA1c (hemoglobin A1c) > 8.0 %
             at screening

          -  Concomitant medication of B12, folate, betaine or choline

          -  Concomitant treatment with glitazone within the past year prior to the study

          -  Subjects with known folate or B12 deficiency

          -  BMI (body mass index) > 40 kg/m2

          -  History of major depression diagnostic and statistical manual of mental disorders
             (DSM-IV) or bipolar disease

          -  Women of childbearing potential: positive urine pregnancy test during screening or
             unwillingness to use an effective form of birth control during the study.

          -  Breastfeeding women

          -  Any condition that, in the opinion of the investigator, does not justify the patient's
             inclusion into the study

          -  Investigational drug intake within one month prior to the study

          -  Active, serious medical disease with likely life-expectancy less than five years

          -  Uncooperative attitude or reasonable likelihood for non-compliance with the protocol
             or any other reason that, in the investigator's opinion, prohibits the inclusion of
             the subject into the study

          -  Legal incapacity or limited legal capacity, or who are incarcerated.

          -  Inability to return for scheduled visits.

          -  Inability to understand and follow the requirements of the protocol in the local
             language