Non Alcoholic Fatty Liver DiseasePhase 3EXPONCT01754714
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 study testing SAMe 1000 mg, SAMe 1500 mg and SAMe 2000 mg in people with Non Alcoholic Fatty Liver Disease, run by Abbott at 32 sites in 4 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Non Alcoholic Fatty Liver Disease
- What is being tested?
- SAMe 1000 mg, SAMe 1500 mg and SAMe 2000 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 108 participants
- Where
- 32 sitesin 4 countries
- Study dates
- Dec 2012to Sep 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 40Show fewer
- 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 locations and contacts
32 sites in 4 countries.
32 sites in 4 countries
Germany9 sites
Site Reference ID 93953
Bonn, 53127
Site Reference ID 93954
Frankfurt, 60594
Site Reference ID 93935
Freiburg im Breisgau, 79106
Site Reference ID 93955
Halle, 06120
Site Reference ID 93917
Hanover, 30625
Site Reference ID 93933
Homburg, 66424
Site Reference ID 94015
Leipzig, 04103
Site Reference ID 93918
Mainz, 55131
Site Reference ID 94014
Ulm, 89081
France8 sites
Site Reference ID 93914
Amiens, 80054
Site Reference ID 93895
Angers, 49933
Site Reference ID 93894
Bobigny, 93009
Site Reference ID 93913
Montpellier, 34295
Site Reference ID 93916
Nice, 06202
Site Reference ID 93915
Paris, 75012
Site Reference ID 93893
Paris, 75651
Site Reference ID 93896
Pessac, 33604
Russia8 sites
Site reference ID ORG-000905
Krasnoyarsk, 660022
Site reference ID ORG-000906
Moscow, 119435
Site reference ID ORG-000900
Nizhny Novgorod, 603126
Site reference ID ORG-000907
Novosibirsk, 630084
Site reference ID ORG-000903
Omsk, 644043
Site reference ID ORG-000920
Rostov-on-Don, 344022
Site reference ID ORG-000904
Samara, 443011
Site reference ID ORG-000901
Stavropol, 355017
Poland7 sites
Site reference ID/Investigator # 109455
Bydgoszcz, 85-030
Site Reference ID 93958
Chorzów, 41-500
Site Reference ID 93973
Krakow, 31-531
Site Reference ID 93956
Lodz, 91-347
Site Reference ID 93957
Mysłowice, 41-400
Site Reference ID 93974
Warsaw, 02-507
Site Reference ID 93975
Wroclaw, 50-220
About this study
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
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
- Being tested
- SAMe 1000 mg, SAMe 1500 mg, SAMe 2000 mg
- Keywords
- Steatohepatitis
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SAMe 1000 mgDrug
1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner
SAMe 1500 mgDrug
1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner
SAMe 2000 mgDrug
2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner
| Study group | Role | What they receive |
|---|---|---|
| 1000 mg SAMe (S-adenosyl-L-methionine) | Experimental | Not described Receives: Drug: SAMe 1000 mg |
| 1500 mg SAMe | Experimental | Not described Receives: Drug: SAMe 1500 mg |
| 2000 mg SAMe | Experimental | Not described Receives: Drug: SAMe 2000 mg |
| No treatment | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Secondary outcomes (18)
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.
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
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
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
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)
Measured: change from baseline at 6 weeks
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.
Measured: change from baseline at 6 weeks
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.
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
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.
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
Peak
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
Time to peak
Measured: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Metabolic Panel (Metabolic Laboratory Parameters)
Fasting plasma insulin
Measured: Change from baseline at 6 weeks
Metabolic Panel (Metabolic Laboratory Parameters)
glycosylated hemoglobin (HbA1c)
Measured: change from baseline at 6 weeks
Metabolic Panel (Metabolic Laboratory Parameters)
Adiponectin
Measured: change from baseline at 6 weeks
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
C-reactive Protein (CRP)
Measured: change from baseline at 6 weeks
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
glutathione in erythrocytes
Measured: change from baseline at 6 weeks
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
oxidative stress marker (isoprostane level)
Measured: change from baseline at 6 weeks
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
Caspase-cleaved cytokeratin (CK 18)
Measured: change from baseline at 6 weeks
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
Hyaluronic acid
Measured: change from baseline at 6 weeks
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.
Measured: 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7*
Hepatic Panel (Liver Laboratory Parameters)
ALT/AST ratio
Measured: change from baseline at 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abbott
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Responsible party
- Sponsor
- Investigators
- Suntje Sander-Struckmeier, PhD, Study director, Abbott
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01754714
- Sponsor's protocol ID
- M13-397
- Other IDs
- 2012-000975-18
- Acronym
- EXPO
- Status last verified
- Jan 2016
- First submitted
- 19 Dec 2012
- Last updated
- 19 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01754714
- Acronym / sponsor ID
- EXPO / M13-397
- Conditions
- Non Alcoholic Fatty Liver Disease
- Keywords
- Steatohepatitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 108 participants (actual)
- Lead sponsor
- AbbottIndustry (pharma, biotech, devices)
- Collaborators
- PPD Development, LP
- Study start
- Dec 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 21 Dec 2012 (estimated)
- Results
- Posted 19 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigation the Effects of Different Doses of SAMe in Subjects with Nonalcoholic Fatty Liver Disease and non-treated matched healthy volunteers as control group
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1000 mg SAMe (S-adenosyl-L-methionine) | Experimental | Drug: SAMe 1000 mg |
| 1500 mg SAMe | Experimental | Drug: SAMe 1500 mg |
| 2000 mg SAMe | Experimental | Drug: SAMe 2000 mg |
| No treatment | No intervention | – |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (40 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SAMe 1000 mg1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner | Drug | 1000 mg SAMe (S-adenosyl-L-methionine) |
| SAMe 1500 mg1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner | Drug | 1500 mg SAMe |
| SAMe 2000 mg2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner | Drug | 2000 mg SAMe |
Primary outcome
Methionine Elimination Half-life Measured in Blood.
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
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.
18 secondary outcomes
Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Hepatic Panel (Liver Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Metabolic Panel (Metabolic Laboratory Parameters)
Time frame: change from baseline at 6 weeks
The Metabolic Clearance Rate Measured in the Blood.
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Methionine Volume of Distribution at Week 7 (L)
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test
Time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*
Metabolic Panel (Metabolic Laboratory Parameters)
Time frame: Change from baseline at 6 weeks
Metabolic Panel (Metabolic Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Metabolic Panel (Metabolic Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
Time frame: change from baseline at 6 weeks
Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)
Time frame: change from baseline at 6 weeks
Area Under Curve (AUC) of Average Methionine Concentration Versus Time Curve
Time frame: 0.5, 1, 1.5, 3, 4, 5, 6, 7.5 and 9 hours *at Week 7*
Hepatic Panel (Liver Laboratory Parameters)
Time frame: change from baseline at 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suntje Sander-Struckmeier, PhD study director
Abbott
32 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing SAMe 1000 mg, SAMe 1500 mg and SAMe 2000 mg in people with Non Alcoholic Fatty Liver Disease, run by Abbott at 32 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in Germany, France, Russia, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Methionine Elimination Half-life Measured in Blood. (time frame: 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2016.