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CompletedNCT01754714EXPOUpdated Feb 19, 2016Results posted

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

A Phase 3 interventional study of SAMe 1000 mg and SAMe 1500 mg in Non Alcoholic Fatty Liver Disease, sponsored by Abbott. Completed at 32 sites in 4 countries. Open to participants aged 18 Years to 99 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-02-19.

Sponsored by Abbott · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
108
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study 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

02

Conditions studied

  • Non Alcoholic Fatty Liver Disease

Keywords

  • Steatohepatitis
03

In context

Liver Diseases

2,081 studies on the registry are indexed under Liver Diseases; 390 are open to participants now.

This study's enrollment of 108 is above the median of 50 across 1,323 interventional studies indexed under Liver Diseases.

Browse Liver Diseases studies →

Lead sponsor

Abbott is the lead sponsor of 350 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
108 participants (actual)

Study arms

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

    Drug: SAMe 1000 mg

  • Experimental
    1500 mg SAMe

    Drug: SAMe 1500 mg

  • Experimental
    2000 mg SAMe

    Drug: SAMe 2000 mg

  • No intervention
    No treatment

Interventions

  • DrugSAMe 1000 mg

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

  • DrugSAMe 1500 mg

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

  • DrugSAMe 2000 mg

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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

Secondary outcomes

  1. 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.

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

  2. 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

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

  3. 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)

    Time frame: change from baseline at 6 weeks

  4. 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.

    Time frame: change from baseline at 6 weeks

  5. 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.

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

  6. 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.

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

  7. 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

    Peak

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

  8. 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

    Time to peak

    Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

  9. Metabolic Panel (Metabolic Laboratory Parameters)

    Fasting plasma insulin

    Time frame: Change from baseline at 6 weeks

  10. Metabolic Panel (Metabolic Laboratory Parameters)

    glycosylated hemoglobin (HbA1c)

    Time frame: change from baseline at 6 weeks

  11. Metabolic Panel (Metabolic Laboratory Parameters)

    Adiponectin

    Time frame: change from baseline at 6 weeks

  12. Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

    C-reactive Protein (CRP)

    Time frame: change from baseline at 6 weeks

  13. Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

    glutathione in erythrocytes

    Time frame: change from baseline at 6 weeks

  14. Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

    oxidative stress marker (isoprostane level)

    Time frame: change from baseline at 6 weeks

  15. Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

    Caspase-cleaved cytokeratin (CK 18)

    Time frame: change from baseline at 6 weeks

  16. Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

    Hyaluronic acid

    Time frame: change from baseline at 6 weeks

  17. 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.

    Time frame: 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7*

  18. Hepatic Panel (Liver Laboratory Parameters)

    ALT/AST ratio

    Time frame: change from baseline at 6 weeks

Other outcomes

  1. Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

    Cytokine profile ( Interleukin-6, IL-8, IL-10 (IL), Tumor Necrosis Factor (TNF -α), monocyte chemoattractant protein (MCP-1), and Granulocyte-colony stimulating factor (G-CSF ).

    Time frame: change from baseline at 6 weeks

  2. 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.

    Time frame: change from baseline at 6 weeks

07

Results

Posted Feb 19, 2016

Participant flow

Participant flow — Overall Study
Milestone1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Started27272628
Completed27262427
Not completed0121

Outcome measures

PrimaryMethionine 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.

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Mean · hour
Methionine Elimination Half-life Measured in Blood.
hour1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Methionine Elimination Half-life Measured in Blood.4.29 ± 1.864.66 ± 1.574.25 ± 1.644.26 ± 1.44
SecondaryFasting 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.

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Mean · mcg/mL
Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.
mcg/mL1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.4.02 ± 0.923.81 ± 0.675.68 ± 10.135.62 ± 8.53
Secondary13 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

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Mean · percentage of recovery
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
percentage of recovery1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
13C methionine breath test recovery at 30 min (%)0.93 ± 0.730.77 ± 0.510.88 ± 0.660.69 ± 0.55
13C methionine breath test recovery at 60 min (%)3.66 ± 1.993.49 ± 1.743.61 ± 1.782.98 ± 1.72
13C methionine breath test recovery at 90 min (%)6.69 ± 2.756.60 ± 2.566.68 ± 2.485.74 ± 2.56
SecondaryHepatic 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)

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · U/L
Hepatic Panel (Liver Laboratory Parameters)
U/L1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
ALP1.9 ± 7.9-0.1 ± 13.73.4 ± 24.1-6.0 ± 16.9
ALT-6.2 ± 19.5-6.3 ± 23.5-4.9 ± 32.2-11.9 ± 33.4
AST-5.1 ± 15.7-3.0 ± 16.5-1.2 ± 10.7-11.6 ± 27.7
GGT-1.1 ± 33.7-10.6 ± 62.7-2.7 ± 35.7-12.3 ± 48.1
SecondaryMetabolic 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.

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · mmol/L
Metabolic Panel (Metabolic Laboratory Parameters)
mmol/L1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Cholesterol-0.131 ± 0.5930.046 ± 0.921-0.265 ± 0.601-0.134 ± 0.659
HDL-0.094 ± 0.166-0.046 ± 0.254-0.098 ± 0.169-0.075 ± 0.188
LDL0.125 ± 0.4520.182 ± 0.762-0.202 ± 0.589-0.112 ± 0.558
HOMA-R0.837 ± 13.2320.127 ± 3.763-1.549 ± 13.3213.432 ± 10.837
Glucose-0.068 ± 0.9680.490 ± 1.486-0.163 ± 1.009-0.121 ± 1.610
Other pre-specifiedImmunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

Cytokine profile ( Interleukin-6, IL-8, IL-10 (IL), Tumor Necrosis Factor (TNF -α), monocyte chemoattractant protein (MCP-1), and Granulocyte-colony stimulating factor (G-CSF ).

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · pg/mL
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
pg/mL1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
IL-6: n= (27,24,23,27)0.0603 ± 2.0263-0.9254 ± 6.4599-1.3194 ± 4.57790.1597 ± 1.6243
IL-8: n= (8,6,7,9)-14.41 ± 41.070.65 ± 13.37-78.73 ± 187.51-6.17 ± 16.94
IL-10: n= (1,2,1,2)0.270 ± NA-0.045 ± 0.106-0.300 ± NA1.600 ± 1.146
TNF-alpha: n= (24,24,20,27)-0.127 ± 0.414-1.083 ± 4.782-0.601 ± 2.136-0.187 ± 1.114
MCP-1: n= (27,25,24,27)-29.75 ± 154.75-20.60 ± 79.71-40.15 ± 96.21-44.51 ± 114.85
G-CSF: n= (5,4,1,0)-20.0 ± 52.8-0.5 ± 9.720.0 ± NANA ± NA
Other pre-specifiedFibrosis 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.

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · scores on a scale
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
scores on a scale1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
ActiTest Score-0.017 ± 0.098-0.022 ± 0.137-0.002 ± 0.168-0.042 ± 0.096
Fibrotest Score0.036 ± 0.0970.028 ± 0.0930.050 ± 0.1250.020 ± 0.068
SecondaryThe 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.

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Mean · L/h
The Metabolic Clearance Rate Measured in the Blood.
L/h1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
The Metabolic Clearance Rate Measured in the Blood.8.86 ± 2.939.83 ± 3.2710.05 ± 4.328.23 ± 2.30
SecondaryMethionine 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.

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Mean · L
Methionine Volume of Distribution at Week 7 (L)
L1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Methionine Volume of Distribution at Week 7 (L)54.40 ± 18.4362.84 ± 14.0464.58 ± 17.778.23 ± 53.98
Secondary13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

Peak

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Mean · Atom %C13
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
Atom %C131000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test1.0972 ± 0.00621.0964 ± 0.00521.0964 ± 0.00531.0949 ± 0.0045
Secondary13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

Time to peak

Time frame:
0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Reported as:
Median · minutes
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
minutes1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test70.0 (50.0 to 80.0)70.0 (60.0 to 90.0)70.0 (50.0 to 80.0)70.0 (60.0 to 90.0)
SecondaryMetabolic Panel (Metabolic Laboratory Parameters)

Fasting plasma insulin

Time frame:
Change from baseline at 6 weeks
Reported as:
Mean · pmol/L
Metabolic Panel (Metabolic Laboratory Parameters)
pmol/L1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Metabolic Panel (Metabolic Laboratory Parameters)0.3 ± 191.0-13.6 ± 115.5-13.1 ± 24869.1 ± 309.0
SecondaryMetabolic Panel (Metabolic Laboratory Parameters)

glycosylated hemoglobin (HbA1c)

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · Percentage
Metabolic Panel (Metabolic Laboratory Parameters)
Percentage1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Metabolic Panel (Metabolic Laboratory Parameters)-0.08 ± 0.28-0.06 ± 0.36-0.05 ± 0.320.02 ± 0.33
SecondaryMetabolic Panel (Metabolic Laboratory Parameters)

Adiponectin

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · mcg/mL
Metabolic Panel (Metabolic Laboratory Parameters)
mcg/mL1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Metabolic Panel (Metabolic Laboratory Parameters)0.754 ± 4.1910.425 ± 1.1990.219 ± 1.6610.045 ± 1.515
SecondaryImmunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

C-reactive Protein (CRP)

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · nmol/L
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
nmol/L1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)-0.79 ± 15.51-0.80 ± 14.90-8.02 ± 20.40-4.80 ± 12.8
SecondaryImmunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

glutathione in erythrocytes

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · mcmol/g
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
mcmol/g1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)-0.24 ± 2.06-0.21 ± 1.010.05 ± 1.41-0.30 ± 1.33
SecondaryImmunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

oxidative stress marker (isoprostane level)

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · ng/mg Crea
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
ng/mg Crea1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)-0.223 ± 0.8010.116 ± 0.6990.290 ± 0.691-0.223 ± 0.641
SecondaryFibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

Caspase-cleaved cytokeratin (CK 18)

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · U/L
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
U/L1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)-126.8 ± 401.1-136.6 ± 257.3-47.0 ± 157.3-143.2 ± 532.5
SecondaryFibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

Hyaluronic acid

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · ng/mL
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
ng/mL1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)4.67 ± 48.522.03 ± 32.269.40 ± 59.633.02 ± 46.56
SecondaryArea 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.

Time frame:
0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7*
Reported as:
Mean · mcg/mL
Area Under Curve (AUC) of Average Methionine Concentration Versus Time Curve
mcg/mL1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Area Under Curve (AUC) of Average Methionine Concentration Versus Time Curve440.09 ± 149.96399.30 ± 148.90425.24 ± 231.88460.57 ± 135.63
SecondaryHepatic Panel (Liver Laboratory Parameters)

ALT/AST ratio

Time frame:
change from baseline at 6 weeks
Reported as:
Mean · Ratio
Hepatic Panel (Liver Laboratory Parameters)
Ratio1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
Hepatic Panel (Liver Laboratory Parameters)-0.02 ± 0.230.01 ± 0.210.03 ± 0.18-0.01 ± 0.27

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
1000 mg SAMe (S-adenosyl-L-methionine)—0/27 (0%)7/27 (25.9%)
1500 mg SAMe—0/27 (0%)4/27 (14.8%)
2000 mg SAMe—0/24 (0%)7/24 (29.2%)
No Treatment—1/28 (3.6%)2/28 (7.1%)
Most frequent serious events
Most frequent serious events
Event1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
head injury and neck injury before start of treatmentInjury, poisoning and procedural complications0/270/270/241/28
Most frequent other events
Most frequent other events
Event1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo Treatment
DIARRHOEAGastrointestinal disorders3/272/274/240/28
Abdominal PainGastrointestinal disorders0/271/273/242/28
HeadacheNervous system disorders2/271/271/240/28
FatigueGeneral disorders2/270/270/240/28

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo TreatmentTotal
<=18 years00000
Between 18 and 65 years2324232191
>=65 years433717
Age, Continuous
Age, Continuous(years)1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo TreatmentTotal
Mean51.2 ± 13.850.0 ± 12.349.5 ± 14.256.6 ± 11.651.9 ± 13.1
Sex: Female, Male
Sex: Female, Male(Participants)1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo TreatmentTotal
Female151091145
Male1217171763
Region of Enrollment
Region of Enrollment(participants)1000 mg SAMe (S-adenosyl-L-methionine)1500 mg SAMe2000 mg SAMeNo TreatmentTotal
Russian Federation565218
Poland326617
France654924
Germany1314111149
08

Study locations

32 sites
  • Site Reference ID 93914
    Amiens, 80054, France
  • Site Reference ID 93895
    Angers, 49933, France
  • Site Reference ID 93894
    Bobigny, 93009, France
  • Site Reference ID 93913
    Montpellier, 34295, France
  • Site Reference ID 93916
    Nice, 06202, France
  • Site Reference ID 93915
    Paris, 75012, France
  • Site Reference ID 93893
    Paris, 75651, France
  • Site Reference ID 93896
    Pessac, 33604, France
  • Site Reference ID 93953
    Bonn, 53127, Germany
  • Site Reference ID 93954
    Frankfurt, 60594, Germany
  • Site Reference ID 93935
    Freiburg, 79106, Germany
  • Site Reference ID 93955
    Halle, 06120, Germany
  • Site Reference ID 93917
    Hannover, 30625, Germany
  • Site Reference ID 93933
    Homburg, 66424, Germany
  • Site Reference ID 94015
    Leipzig, 04103, Germany
  • Site Reference ID 93918
    Mainz, 55131, Germany
  • Site Reference ID 94014
    Ulm, 89081, Germany
  • Site reference ID/Investigator # 109455
    Bydgoszcz, 85-030, Poland
  • Site Reference ID 93958
    Chorzow, 41-500, Poland
  • Site Reference ID 93973
    Krakow, 31-531, Poland
  • Site Reference ID 93956
    Lodz, 91-347, Poland
  • Site Reference ID 93957
    Myslowice, 41-400, Poland
  • Site Reference ID 93974
    Warsaw, 02-507, Poland
  • Site Reference ID 93975
    Wroclaw, 50-220, Poland
  • Site reference ID ORG-000905
    Krasnoyarsk, 660022, Russian Federation
  • Site reference ID ORG-000906
    Moscow, 119435, Russian Federation
  • Site reference ID ORG-000900
    Nizhniy Novgorod, 603126, Russian Federation
  • Site reference ID ORG-000907
    Novosibirsk, 630084, Russian Federation
  • Site reference ID ORG-000903
    Omsk, 644043, Russian Federation
  • Site reference ID ORG-000920
    Rostov-on-Don, 344022, Russian Federation
  • Site reference ID ORG-000904
    Samara, 443011, Russian Federation
  • Site reference ID ORG-000901
    Stavropol, 355017, Russian Federation
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 19, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01754714
Lead sponsor
Abbott
Collaborators
PPD DEVELOPMENT, LP
Responsible party
Sponsor
First posted
Dec 21, 2012
Start date
Dec 2012
Primary completion
Sep 2014
Completion
Sep 2014
Results posted
Feb 19, 2016
Last update
Feb 19, 2016

Study contacts

Suntje Sander-Struckmeier, PhD
study director · Abbott

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jan 2016. You cannot join it, but the record below documents what was studied.

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