Clinical trial NCT01754714: 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
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Alcoholic Fatty Liver Disease
Keywords: Steatohepatitis
Lead sponsor: Abbott
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2012-12-21
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Methionine Elimination Half-life Measured in Blood.
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Secondary outcomes:
measure: Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
measure: 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
measure: Hepatic Panel (Liver Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Metabolic Panel (Metabolic Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: The Metabolic Clearance Rate Measured in the Blood.
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
measure: Methionine Volume of Distribution at Week 7 (L)
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
measure: 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
measure: 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
timeFrame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
measure: Metabolic Panel (Metabolic Laboratory Parameters)
timeFrame: Change from baseline at 6 weeks
measure: Metabolic Panel (Metabolic Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Metabolic Panel (Metabolic Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
timeFrame: change from baseline at 6 weeks
measure: Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
timeFrame: change from baseline at 6 weeks
measure: Area Under Curve (AUC) of Average Methionine Concentration Versus Time Curve
timeFrame: 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7*
measure: Hepatic Panel (Liver Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
Other outcomes:
measure: Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
timeFrame: change from baseline at 6 weeks
measure: Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
timeFrame: change from baseline at 6 weeks
Locations:
city: Amiens
country: France
facility: Site Reference ID 93914
city: Angers
country: France
facility: Site Reference ID 93895
city: Bobigny
country: France
facility: Site Reference ID 93894
city: Montpellier
country: France
facility: Site Reference ID 93913
city: Nice
country: France
facility: Site Reference ID 93916
city: Paris
country: France
facility: Site Reference ID 93915
city: Paris
country: France
facility: Site Reference ID 93893
city: Pessac
country: France
facility: Site Reference ID 93896
city: Bonn
country: Germany
facility: Site Reference ID 93953
city: Frankfurt
country: Germany
facility: Site Reference ID 93954
city: Freiburg
country: Germany
facility: Site Reference ID 93935
city: Halle
country: Germany
facility: Site Reference ID 93955
city: Hannover
country: Germany
facility: Site Reference ID 93917
city: Homburg
country: Germany
facility: Site Reference ID 93933
city: Leipzig
country: Germany
facility: Site Reference ID 94015
city: Mainz
country: Germany
facility: Site Reference ID 93918
city: Ulm
country: Germany
facility: Site Reference ID 94014
city: Bydgoszcz
country: Poland
facility: Site reference ID/Investigator # 109455
city: Chorzow
country: Poland
facility: Site Reference ID 93958
city: Krakow
country: Poland
facility: Site Reference ID 93973
city: Lodz
country: Poland
facility: Site Reference ID 93956
city: Myslowice
country: Poland
facility: Site Reference ID 93957
city: Warsaw
country: Poland
facility: Site Reference ID 93974
city: Wroclaw
country: Poland
facility: Site Reference ID 93975
city: Krasnoyarsk
country: Russian Federation
facility: Site reference ID ORG-000905
city: Moscow
country: Russian Federation
facility: Site reference ID ORG-000906
city: Nizhniy Novgorod
country: Russian Federation
facility: Site reference ID ORG-000900
city: Novosibirsk
country: Russian Federation
facility: Site reference ID ORG-000907
city: Omsk
country: Russian Federation
facility: Site reference ID ORG-000903
city: Rostov-on-Don
country: Russian Federation
facility: Site reference ID ORG-000920
city: Samara
country: Russian Federation
facility: Site reference ID ORG-000904
city: Stavropol
country: Russian Federation
facility: Site reference ID ORG-000901
Study officials:
affiliation: Abbott
name: Suntje Sander-Struckmeier, PhD
role: STUDY_DIRECTOR
References: