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

NCT ID: NCT01754714

Last Updated: 2016-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2014-09-30

Brief 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

Conditions

Non Alcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

SAMe 1000 mg

Intervention Type: DRUG

1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner

1500 mg SAMe

Group Type: EXPERIMENTAL

SAMe 1500 mg

Intervention Type: DRUG

1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner

2000 mg SAMe

Group Type: EXPERIMENTAL

SAMe 2000 mg

Intervention Type: DRUG

2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner

No treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

SAMe 1000 mg

1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner

Intervention Type: DRUG

SAMe 1500 mg

1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner

Intervention Type: DRUG

SAMe 2000 mg

2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

Abbott

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suntje Sander-Struckmeier, PhD

Role: STUDY_DIRECTOR

Abbott

Locations

Site Reference ID 93914

Amiens, , France

Site Reference ID 93895

Angers, , France

Site Reference ID 93894

Bobigny, , France

Site Reference ID 93913

Montpellier, , France

Site Reference ID 93916

Nice, , France

Site Reference ID 93915

Paris, , France

Site Reference ID 93893

Paris, , France

Site Reference ID 93896

Pessac, , France

Site Reference ID 93953

Bonn, , Germany

Site Reference ID 93954

Frankfurt, , Germany

Site Reference ID 93935

Freiburg im Breisgau, , Germany

Site Reference ID 93955

Halle, , Germany

Site Reference ID 93917

Hanover, , Germany

Site Reference ID 93933

Homburg, , Germany

Site Reference ID 94015

Leipzig, , Germany

Site Reference ID 93918

Mainz, , Germany

Site Reference ID 94014

Ulm, , Germany

Site reference ID/Investigator # 109455

Bydgoszcz, , Poland

Site Reference ID 93958

Chorzów, , Poland

Site Reference ID 93973

Krakow, , Poland

Site Reference ID 93956

Lodz, , Poland

Site Reference ID 93957

Mysłowice, , Poland

Site Reference ID 93974

Warsaw, , Poland

Site Reference ID 93975

Wroclaw, , Poland

Site reference ID ORG-000905

Krasnoyarsk, , Russia

Site reference ID ORG-000906

Moscow, , Russia

Site reference ID ORG-000900

Nizhny Novgorod, , Russia

Site reference ID ORG-000907

Novosibirsk, , Russia

Site reference ID ORG-000903

Omsk, , Russia

Site reference ID ORG-000920

Rostov-on-Don, , Russia

Site reference ID ORG-000904

Samara, , Russia

Site reference ID ORG-000901

Stavropol, , Russia

Countries

France; Germany; Poland; Russia

Other Identifiers

2012-000975-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M13-397

Identifier Type: -

Identifier Source: org_study_id