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 (EXPO)

Abbott

Status and phase: Completed; Phase 3

Conditions: Non Alcoholic Fatty Liver Disease

Treatments: Drug: SAMe 1500 mg; Drug: SAMe 2000 mg; Drug: SAMe 1000 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01754714

M13-397

2012-000975-18 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 108 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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108 participants in 4 patient groups

1000 mg SAMe (S-adenosyl-L-methionine)

Experimental group

Treatment:

Drug: SAMe 1000 mg

1500 mg SAMe

Experimental group

Treatment:

Drug: SAMe 1500 mg

2000 mg SAMe

Experimental group

Treatment:

Drug: SAMe 2000 mg

No treatment

No Intervention group