Non Alcoholic Fatty Liver Disease Clinical Trial
— EXPOOfficial title:
Open-label, Randomized, Parallel-Group, Exploratory Study to Investigate the Effects of Different Doses of S-adenosyl-L-methionine (SAMe) in Subjects With Nonalcoholic Steatohepatitis (NASH) and Non-treated Matched Healthy Volunteers as Control Group
Verified date | January 2016 |
Source | Abbott |
Contact | n/a |
Is FDA regulated | No |
Health authority | Germany: Federal Institute for Drugs and Medical Devices |
Study type | Interventional |
Investigation the Effects of Different Doses of SAMe in Subjects with Nonalcoholic Fatty Liver Disease and non-treated matched healthy volunteers as control group
Status | Completed |
Enrollment | 108 |
Est. completion date | September 2014 |
Est. primary completion date | September 2014 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Both |
Age group | 18 Years to 99 Years |
Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
France | 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 93893 | Paris | |
France | Site Reference ID 93915 | Paris | |
France | Site Reference ID 93896 | Pessac | |
Germany | Site Reference ID 93953 | Bonn | |
Germany | Site Reference ID 93954 | Frankfurt | |
Germany | Site Reference ID 93935 | Freiburg | |
Germany | Site Reference ID 93955 | Halle | |
Germany | Site Reference ID 93917 | Hannover | |
Germany | Site Reference ID 93933 | Homburg | |
Germany | Site Reference ID 94015 | Leipzig | |
Germany | Site Reference ID 93918 | Mainz | |
Germany | Site Reference ID 94014 | Ulm | |
Poland | Site reference ID/Investigator # 109455 | Bydgoszcz | |
Poland | Site Reference ID 93958 | Chorzow | |
Poland | Site Reference ID 93973 | Krakow | |
Poland | Site Reference ID 93956 | Lodz | |
Poland | Site Reference ID 93957 | Myslowice | |
Poland | Site Reference ID 93974 | Warsaw | |
Poland | Site Reference ID 93975 | Wroclaw | |
Russian Federation | Site reference ID ORG-000905 | Krasnoyarsk | |
Russian Federation | Site reference ID ORG-000906 | Moscow | |
Russian Federation | Site reference ID ORG-000900 | Nizhniy Novgorod | |
Russian Federation | Site reference ID ORG-000907 | Novosibirsk | |
Russian Federation | Site reference ID ORG-000903 | Omsk | |
Russian Federation | Site reference ID ORG-000920 | Rostov-on-Don | |
Russian Federation | Site reference ID ORG-000904 | Samara | |
Russian Federation | Site reference ID ORG-000901 | Stavropol |
Lead Sponsor | Collaborator |
---|---|
Abbott | PPD |
France, Germany, Poland, Russian Federation,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters) | Cytokine profile ( Interleukin-6, IL-8, IL-10 (IL), Tumor Necrosis Factor (TNF -a), monocyte chemoattractant protein (MCP-1), and Granulocyte-colony stimulating factor (G-CSF ). | change from baseline at 6 weeks | No |
Other | Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers) | Non-invasive test for liver disease (ActiTest)/Fibrotest FibroTest® : diagnoses hepatic fibrosis ActiTest® : assesses viral necro-inflammatory activity Scores between 0 and 1, the higher the score the worse The FibroTest score is calculated from the results of a six-parameter blood test, combining six serum markers with the age and gender of the patient:Alpha-2-macroglobulin, Haptoglobin, Apolipoprotein A1, Gamma-glutamyl transpeptidase (GGT), Total bilirubin, and Alanine transaminase (ALT). ALT is used in a second assessment called ActiTest that is part of FibroTest. |
change from baseline at 6 weeks | No |
Primary | Methionine Elimination Half-life Measured in Blood. | After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine. | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve. | After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine. | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test | parameters cumulative percentage dose of 13 carbon recovered after 30, 60, 90 minutes (cPDR30, cPDR60, cPDR 90) will be evaluated | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | Hepatic Panel (Liver Laboratory Parameters) | Serum Total Bilirubin (STB), Serum Conjugated Bilirubin (SCB), liver-alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), Gamma Glutamyl Transpeptidase (GGT) | change from baseline at 6 weeks | No |
Secondary | Metabolic Panel (Metabolic Laboratory Parameters) | Fasting lipid profile (cholesterol, HDL (High Density Lipoprotein), LDL (Low Density Lipoprotein)), amino acid profile, homeostasis model assessment (HOMA-R) and fasting glucose. | change from baseline at 6 weeks | No |
Secondary | The Metabolic Clearance Rate Measured in the Blood. | After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine. | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | Methionine Volume of Distribution at Week 7 (L) | After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine. | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test | Peak | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test | Time to peak | 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7* | No |
Secondary | Metabolic Panel (Metabolic Laboratory Parameters) | Fasting plasma insulin | Change from baseline at 6 weeks | No |
Secondary | Metabolic Panel (Metabolic Laboratory Parameters) | glycosylated hemoglobin (HbA1c) | change from baseline at 6 weeks | No |
Secondary | Metabolic Panel (Metabolic Laboratory Parameters) | Adiponectin | change from baseline at 6 weeks | No |
Secondary | Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters) | C-reactive Protein (CRP) | change from baseline at 6 weeks | No |
Secondary | Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters) | glutathione in erythrocytes | change from baseline at 6 weeks | No |
Secondary | Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters) | oxidative stress marker (isoprostane level) | change from baseline at 6 weeks | No |
Secondary | Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers) | Caspase-cleaved cytokeratin (CK 18) | change from baseline at 6 weeks | No |
Secondary | Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers) | Hyaluronic acid | change from baseline at 6 weeks | No |
Secondary | Area Under Curve (AUC) of Average Methionine Concentration Versus Time Curve | After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine. | 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7* | No |
Secondary | Hepatic Panel (Liver Laboratory Parameters) | ALT/AST ratio | change from baseline at 6 weeks | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
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