Alcoholic HepatitisPhase 2RCT SAMeNCT00851981
Randomized, Controlled Trial of S-adenosylmethionine in Alcoholic Liver Disease
A Phase 2 study testing SAMe in people with Alcoholic Hepatitis, run by Loma Linda University at 1 site in United States.
Trial summary
Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country. There is currently no treatment for chronic alcoholic liver disease other than abstinence. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholic Hepatitis
- What is being tested?
- SAMe
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to May 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be chronic alcohol users, defined by a history of ethanol consumption on average > 40g/day for women and 60g/day for men for at least 1 year before inclusion.
- The presumptive diagnosis for alcoholic hepatitis will be: recent binge drinking; compatible physical findings (one or more: jaundice, enlarged liver, hepatic bruit, abdominal pain, loss of appetite, nausea); and a compatible biochemical profile (moderate elevation of AST over ALT, elevated total serum bilirubin); or a liver-spleen colloid scan suggestive of reticulo-endothelial redistribution and hepatic arterialization.
- The diagnosis of alcoholic hepatitis must be confirmed on liver biopsy, showing typical features of acute sclerosing hyaline necrosis 70.
- The degree of portal fibrosis as determined on liver biopsy, graded according to the Knodell score-modified by Ishak 71 must be less than or equal to 5 out of a possible score of 6, 6 indicating cirrhosis.
- The alcoholic hepatitis must be "stable", i.e. not requiring treatment by either pentoxifylline 72 or prednisone, with a Maddrey Score 73 {(PTpatient - PTcontrol) x 4.6 + TBmg/dL} < 32.
- Patients must be willing to participate in the trial, remain abstinent to alcohol, and compliant to the treatment regimen, and undergo a post-treatment liver biopsy.
Who cannot join
- Patients who have either compensated cirrhosis (biopsy proven) or a clinical picture of severe cirrhosis defined as Child's class C and/or with a recent history (within one month) of decompensated liver disease (history of ascites, encephalopathy or variceal bleeding within one month of trial entry). These patients have reduced life expectancy below one year and are most often severely coagulopathic and cannot be biopsied.
- Patients who have severe acute alcoholic hepatitis of poor prognosis defined as a Maddrey Score > 32. These patients have a mortality rate of 50% during their hospitalization period when untreated by either prednisone or pentoxifylline.
- Patients who are receiving hepatotropic treatments such as colchicine, penicillamine, corticosteroids, ursodeoxycholic acid, and pentoxifylline.
- Patients who are receiving known hepatotoxic long-term treatments such as NSAIDs, statins, neuroleptics, certain anti-convulsive medications, or high-dose acetaminophen.
- Patients suspected of having hepatocellular carcinoma.
- Patients who have contra-indications to liver biopsy.
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- Patients who have a liver biopsy that does not yield sufficient specimen for analyses.
- Patients who have untreated deficiencies of folic acid, vitamin B6 or B12.
- Patients who have chronic active Hepatitis B or C, hemochromatosis, autoimmune hepatitis, or a cholangiopathy.
- Patients with psychotic disorders, and in particular manic depression (contra indication to SAMe treatment).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Oral S-Adenosylmethionine Administration on Abnormalities of Hepatic Methionine Metabolism and Disease Progression in Alcoholic Liver Disease. A Randomized, Double Blind, Placebo-controlled Trial
Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country. There is currently no treatment for chronic alcoholic liver disease other than abstinence. Hepatic methionine metabolism is abnormal in these patients and one of the consequences is depletion of S-adenosylmethionine (SAMe) levels, which can affect numerous important cellular processes. SAMe has been increasingly utilized for the treatment of liver diseases although the protective mechanisms remain unclear. A recent randomized double-blind trial using SAMe in patients with alcoholic liver disease and found improvement in 2-year survival in those with less advanced liver disease. However, important changes in methionine metabolism and histological changes were not included in the study. Aim: The goal of this study is to determine the effect of SAMe administration on key metabolic abnormalities of the methionine cycle and on the recovery from alcoholic liver disease.
Read the detailed description
Methods: This is a randomized, double blind, placebo-controlled trial. Thirty patients with stable alcoholic hepatitis (Maddrey Score < 32) without cirrhosis who meet entry criteria will receive either 400 mg of SAMe (n=15) or placebo (n=15) three times a day for the duration of one year. History, physical assessment, various blood tests and a liver biopsy will be performed prior to treatment. Patients will have repeat blood tests on subsequent follow-up visits every month for the first two months, then every two months thereafter. They will also be encouraged to abstain from alcohol during these visits. A post-treatment liver biopsy will be obtained at the end of the trial. The primary outcome parameters include serum homocysteine, SAMe and TNFalpha levels, and the expression of key hepatic enzymes of the methionine cycle and of hepatic SAMe and glutathione levels. Histological progression of alcoholic liver disease, clinical and biochemical indices of liver disease, and quality of life assessment will also be examined.
- Conditions
- Alcoholic Hepatitis
- Being tested
- Placebo, SAMe
- Keywords
- Alcohol Liver Disease
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
TID
SAMeDietary supplement
300 mg TID
| Study group | Role | What they receive |
|---|---|---|
| 1 | Placebo comparator | Not described Receives: Other: Placebo |
| SAMe | Active comparator | Not described Receives: Dietary Supplement: SAMe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma homocysteine, hepatic GSH and SAMe levels and hepatic expression of TNF,MAT1A,MAT2A,MS,CBS and BHMT.
Measured: 1 year
Secondary outcomes (1)
Changes in routine liver pathology,c-myc expression and markers of apoptosis, stellate cell activation and hepatocyte proliferation.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2009 (estimated)
- Study startOct 2008
- Primary completionMay 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by Loma Linda UniversityThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Loma Linda University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Investigators
- Michel H Mendler, M.D., Principal investigator, Loma Linda Univeristy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00851981
- Sponsor's protocol ID
- 55302
- Other IDs
- 1R21AA014269-01A1
- Acronym
- RCT SAMe
- Status last verified
- Sep 2010
- First submitted
- 24 Feb 2009
- Last updated
- 13 Sep 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral S-Adenosylmethionine Administration on Abnormalities of Hepatic Methionine Metabolism and Disease Progression in Alcoholic Liver Disease. A Randomized, Double Blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT00851981
- Acronym / sponsor ID
- RCT SAMe / 55302
- Conditions
- Alcoholic Hepatitis
- Keywords
- Alcohol Liver Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Loma Linda UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Oct 2008
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 26 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Alcoholic liver disease is one of the most important causes of chronic liver disease in this country. There is currently no treatment for chronic alcoholic liver disease other than abstinence. Hepatic methionine metabolism is abnormal in these patients and one of the consequences is depletion of S-adenosylmethionine (SAMe) levels, which can affect numerous important cellular processes. SAMe has been increasingly utilized for the treatment of liver diseases although the protective mechanisms remain unclear. A recent randomized double-blind trial using SAMe in patients with alcoholic liver disease and found improvement in 2-year survival in those with less advanced liver disease. However, important changes in methionine metabolism and histological changes were not included in the study. Aim: The goal of this study is to determine the effect of SAMe administration on key metabolic abnormalities of the methionine cycle and on the recovery from alcoholic liver disease.
Detailed description
Methods: This is a randomized, double blind, placebo-controlled trial. Thirty patients with stable alcoholic hepatitis (Maddrey Score < 32) without cirrhosis who meet entry criteria will receive either 400 mg of SAMe (n=15) or placebo (n=15) three times a day for the duration of one year. History, physical assessment, various blood tests and a liver biopsy will be performed prior to treatment. Patients will have repeat blood tests on subsequent follow-up visits every month for the first two months, then every two months thereafter. They will also be encouraged to abstain from alcohol during these visits. A post-treatment liver biopsy will be obtained at the end of the trial. The primary outcome parameters include serum homocysteine, SAMe and TNFalpha levels, and the expression of key hepatic enzymes of the methionine cycle and of hepatic SAMe and glutathione levels. Histological progression of alcoholic liver disease, clinical and biochemical indices of liver disease, and quality of life assessment will also be examined.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Placebo comparator | Other: Placebo |
| SAMe | Active comparator | Dietary Supplement: SAMe |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must be chronic alcohol users, defined by a history of ethanol consumption on average > 40g/day for women and 60g/day for men for at least 1 year before inclusion.
- The presumptive diagnosis for alcoholic hepatitis will be: recent binge drinking; compatible physical findings (one or more: jaundice, enlarged liver, hepatic bruit, abdominal pain, loss of appetite, nausea); and a compatible biochemical profile (moderate elevation of AST over ALT, elevated total serum bilirubin); or a liver-spleen colloid scan suggestive of reticulo-endothelial redistribution and hepatic arterialization.
- The diagnosis of alcoholic hepatitis must be confirmed on liver biopsy, showing typical features of acute sclerosing hyaline necrosis 70.
- The degree of portal fibrosis as determined on liver biopsy, graded according to the Knodell score-modified by Ishak 71 must be less than or equal to 5 out of a possible score of 6, 6 indicating cirrhosis.
- The alcoholic hepatitis must be "stable", i.e. not requiring treatment by either pentoxifylline 72 or prednisone, with a Maddrey Score 73 {(PTpatient - PTcontrol) x 4.6 + TBmg/dL} < 32.
Key exclusion criteria (10 listed)
- Patients who have either compensated cirrhosis (biopsy proven) or a clinical picture of severe cirrhosis defined as Child's class C and/or with a recent history (within one month) of decompensated liver disease (history of ascites, encephalopathy or variceal bleeding within one month of trial entry). These patients have reduced life expectancy below one year and are most often severely coagulopathic and cannot be biopsied.
- Patients who have severe acute alcoholic hepatitis of poor prognosis defined as a Maddrey Score > 32. These patients have a mortality rate of 50% during their hospitalization period when untreated by either prednisone or pentoxifylline.
- Patients who are receiving hepatotropic treatments such as colchicine, penicillamine, corticosteroids, ursodeoxycholic acid, and pentoxifylline.
- Patients who are receiving known hepatotoxic long-term treatments such as NSAIDs, statins, neuroleptics, certain anti-convulsive medications, or high-dose acetaminophen.
- Patients suspected of having hepatocellular carcinoma.
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 |
|---|---|---|
| PlaceboTID | Other | 1 |
| SAMe300 mg TID | Dietary supplement | SAMe |
Primary outcome
Change in plasma homocysteine, hepatic GSH and SAMe levels and hepatic expression of TNF,MAT1A,MAT2A,MS,CBS and BHMT.
Time frame: 1 year
1 secondary outcome
Changes in routine liver pathology,c-myc expression and markers of apoptosis, stellate cell activation and hepatocyte proliferation.
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2010.
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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.
Michel H Mendler, M.D. principal investigator
Loma Linda Univeristy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SAMe in people with Alcoholic Hepatitis, run by Loma Linda University at 1 site in United States.
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 6 inclusion and 10 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 13 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in plasma homocysteine, hepatic GSH and SAMe levels and hepatic expression of TNF,MAT1A,MAT2A,MS,CBS and BHMT. (time frame: 1 year). 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 13 Sep 2010.