Liver Cirrhosis, BiliaryPhase 2NCT00125281
SAMe to Treat Biliary Cirrhosis Symptoms
A Phase 2 study testing S-adenosyl-methionine (SAMe) capsules in people with Liver Cirrhosis, Biliary, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Liver Cirrhosis, Biliary
- What is being tested?
- S-adenosyl-methionine (SAMe) capsules
- Type of treatment
- Pill or oral medicine
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2005to 2 Jul 2008
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age at entry at least 21 years old.
- Pathologically diagnosed primary biliary cirrhosis (made by a liver biopsy performed within 10 years of enrollment) with receipt of stable doses of ursodiol for at least 6 months before enrollment. The dose of urosodiol will be adjusted to achieve stable serum liver enzymes levels.
- Symptoms of itching or fatigue or both. The presence of symptoms will be verified by medical history, symptom questionnaire and visual analogue scales (results greater than 20 mm) on at least two screening visits.
- Written informed consent.
Who cannot join
- Evidence of another form of liver disease.
- Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg) in serum.
- Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum.
- Primary sclerosing cholangitis as defined by liver histology.
- Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
- Autoimmune hepatitis as defined by antinuclear antibody (ANA) of 3 EU or greater (ELISA) and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy for autoimmune hepatitis.
Show all 19Show fewer
- Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than or equal to 250 ng/ml for women will undergo genetic testing for C282Y and H63D.
- Drug induced liver disease as defined on the basis of typical exposure and history.
- Bile duct obstruction as suggested by imaging studies done within the previous six months.
- Decompensated liver disease as defined by a Child-Pugh score of 7 or greater.
- Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease including depression, malignancy and any other conditions that in the opinion of the investigator would preclude treatment. Patients who are suffering from severe depression defined by a score of greater than or equal to 25 in CES-D screening test will not be eligible for enrollment.
- Known HIV infection.
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.
- Pregnancy, lactation or inability to practice adequate contraception in women in child bearing age.
- Evidence of hepatocellular carcinoma as shown by a liver mass on imaging studies or alphafetoprotein levels greater than 200 ng/ml.
- Any other condition, which in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study.
- History of hypersensitivity reactions to S-adenosyl methionine.
- Serum creatinine greater than 1.5mg/dl in men and greater than 1.4 mg/dl for women.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: S-Adenosyl Methionine for Symptomatic Treatment of Primary Biliary Cirrhosis
This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury.
Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale.
Read more
Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe.
After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.
Read the detailed description
To assess the efficacy of S-adenosyl methionine (SAMe) in symptomatic relief of primary biliary cirrhosis (PBC), we will treat up to 50 patients with either SAM-e (800 mg BID) or placebo for 12 weeks in a cross-over, double-blind placebo-controlled study.
S-adenosyl methionine is a nutritional supplement which is available as an over-the-counter formula and is used for treatment of depression and arthritic pain. SAMe is produced in virtually all cells and participates in many biochemical pathways as a major methyl contributor. Intracellular levels of SAMe are often decreased in advanced liver disease. At present SAMe is undergoing extensive evaluation in a large multicenter, randomized controlled trial as an adjunctive therapy of alcoholic liver disease. SAMe has also been evaluated in patients with intrahepatic cholestasis and cholestasis of pregnancy with promising effects of relieving pruritus and fatigue and improving serum liver associated enzymes.
In this study, we will recruit patients with PBC who have pruritus or fatigue despite therapy with ursodiol (the currently recommended therapy of PBC which is partially effective in relieving pruritus and fatigue). After medical evaluation and a brief period of monitoring, patients will be randomized to receive either SAMe or placebo given in oral form in similar appearing capsules twice daily. Patients will be followed at regular intervals for symptoms as monitored by validated questionnaires as well as for side effects and serum biochemical and hematological tests. After 12 weeks, therapy will be withdrawn for 2 weeks and patients will then be switched to the alternative capsules, either SAMe or placebo, for another 12 weeks. The primary endpoints of therapy will be improvements in symptoms of pruritus or fatigue or both. Secondary endpoints will be improvements in serum biochemical liver related enzymes.
- Conditions
- Liver Cirrhosis, Biliary
- Being tested
- S-adenosyl-methionine (SAMe) capsules
- Keywords
- Fatigue, Cirrhosis, S-Adenosyl Methionine, Primary Biliary Cirrhosis, Pruritus, Symptomatic Releif, Serum Liver-Related Enzymes, PBC, Liver Disease
- Medical subject headings
- Liver Cirrhosis, Biliary, Fatigue, Fibrosis, Pruritus, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-adenosyl-methionine (SAMe) capsulesDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy.
Measured: 12 weeks of therapy
Secondary outcomes (1)
Improvement in serum alanine aminotransferase and alkaline phosphatase.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2005 (estimated)
- Study start25 Jul 2005
- Primary completion31 Jul 2007
- Study completion2 Jul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver Cirrhosis, BiliaryStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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
- Crossover
- Masking
- Double blind
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00125281
- Sponsor's protocol ID
- 050207
- Other IDs
- 05-DK-0207
- Status last verified
- 2 Jul 2008
- First submitted
- 29 Jul 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
LLOYD-THOMAS HG, SHERLOCK S. Testosterone therapy for the pruritus of obstructive jaundice. Br Med J. 1952 Dec 13;2(4797):1289-91. doi: 10.1136/bmj.2.4797.1289. No abstract available.
PubMed 12997743
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- S-Adenosyl Methionine for Symptomatic Treatment of Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT00125281
- Acronym / sponsor ID
- 050207
- Conditions
- Liver Cirrhosis, Biliary
- Keywords
- Fatigue, Cirrhosis, S-Adenosyl Methionine, Primary Biliary Cirrhosis, Pruritus, Symptomatic Releif, Serum Liver-Related Enzymes, PBC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 50 participants
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 25 Jul 2005
- Primary completion
- 31 Jul 2007 (actual)
- Study completion
- 2 Jul 2008 (actual)
- First posted
- 29 Jul 2005 (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.
This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury.
Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale.
Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe.
After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.
Detailed description
To assess the efficacy of S-adenosyl methionine (SAMe) in symptomatic relief of primary biliary cirrhosis (PBC), we will treat up to 50 patients with either SAM-e (800 mg BID) or placebo for 12 weeks in a cross-over, double-blind placebo-controlled study.
S-adenosyl methionine is a nutritional supplement which is available as an over-the-counter formula and is used for treatment of depression and arthritic pain. SAMe is produced in virtually all cells and participates in many biochemical pathways as a major methyl contributor. Intracellular levels of SAMe are often decreased in advanced liver disease. At present SAMe is undergoing extensive evaluation in a large multicenter, randomized controlled trial as an adjunctive therapy of alcoholic liver disease. SAMe has also been evaluated in patients with intrahepatic cholestasis and cholestasis of pregnancy with promising effects of relieving pruritus and fatigue and improving serum liver associated enzymes.
In this study, we will recruit patients with PBC who have pruritus or fatigue despite therapy with ursodiol (the currently recommended therapy of PBC which is partially effective in relieving pruritus and fatigue). After medical evaluation and a brief period of monitoring, patients will be randomized to receive either SAMe or placebo given in oral form in similar appearing capsules twice daily. Patients will be followed at regular intervals for symptoms as monitored by validated questionnaires as well as for side effects and serum biochemical and hematological tests. After 12 weeks, therapy will be withdrawn for 2 weeks and patients will then be switched to the alternative capsules, either SAMe or placebo, for another 12 weeks. The primary endpoints of therapy will be improvements in symptoms of pruritus or fatigue or both. Secondary endpoints will be improvements in serum biochemical liver related enzymes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age at entry at least 21 years old.
- Pathologically diagnosed primary biliary cirrhosis (made by a liver biopsy performed within 10 years of enrollment) with receipt of stable doses of ursodiol for at least 6 months before enrollment. The dose of urosodiol will be adjusted to achieve stable serum liver enzymes levels.
- Symptoms of itching or fatigue or both. The presence of symptoms will be verified by medical history, symptom questionnaire and visual analogue scales (results greater than 20 mm) on at least two screening visits.
- Written informed consent.
Key exclusion criteria (19 listed)
- Evidence of another form of liver disease.
- Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg) in serum.
- Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum.
- Primary sclerosing cholangitis as defined by liver histology.
- Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease.
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 |
|---|---|---|
| S-adenosyl-methionine (SAMe) capsules | Drug | – |
Primary outcome
Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy.
Time frame: 12 weeks of therapy
1 secondary outcome
Improvement in serum alanine aminotransferase and alkaline phosphatase.
Time frame: 12 weeks
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 12997743LLOYD-THOMAS HG, SHERLOCK S. Testosterone therapy for the pruritus of obstructive jaundice. Br Med J. 1952 Dec 13;2(4797):1289-91. doi: 10.1136/bmj.2.4797.1289. No abstract available.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 S-adenosyl-methionine (SAMe) capsules in people with Liver Cirrhosis, Biliary, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 4 inclusion and 19 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: stopped early, as of the sponsor's last update on 2 Jul 2017. 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. 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 was stopped early. Results are not available in the source record.
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?
Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy. (time frame: 12 weeks of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00125281, which also lists 1 linked publication.
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 2 Jul 2017.