Primary Biliary CirrhosisPhase 4NCT02557360
Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis
A Phase 4 study testing S-adenosyl-L-methionine in people with Primary Biliary Cirrhosis, run by Pomeranian Medical University Szczecin at 2 sites in Poland.
Trial summary
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder which may lead to several symptoms such as intractable pruritus or chronic fatigue, significantly impairing patients quality of life. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Primary Biliary Cirrhosis
- What is being tested?
- S-adenosyl-L-methionine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesPoland
- Study dates
- Nov 2015to Mar 2017
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- primary biliary cirrhosis diagnosed with EASL criteria;
- treatment with UDCA at least 3 months.
Who cannot join
- overlap syndromes (i.e. autoimmune hepatitis), viral hepatitis;
- decompensated liver cirrhosis (Child-Pugh class B-C);
- other diseases that can affect quality of life and mood: decompensated diabetes mellitus, renal insufficiency requiring dialyses, malignancy, heart failure ≥ New York Heart Association (NYHA) II, rheumatoid arthritis, asthma, mood disorders, depression;
- treatment with: steroids, statins, rifampicin, antidepressants.
Trial locations and contacts
2 sites in 1 country.
About this study
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder which may lead to several symptoms such as intractable pruritus or chronic fatigue, significantly impairing patients quality of life. Recent studies show, that chronic liver diseases are associated with an acquired deficiency of S-adenosyl-L-methionine (SAMe) synthetase, responsible for the synthesis of SAMe from methionine. SAMe deficiency is associated with impaired detoxification and hepatoprotection and exacerbate liver injury. Supplementation with SAMe has proven useful in several liver diseases.
The study group will include 20 patients with PBC diagnosed with European Association for the Study of the Liver (EASL) criteria, who have been already treated with ursodeoxycholic acid (UDCA). They will receive SAMe in the dose of 1600 mg bd over the period of 6 months. Both clinical and laboratory aspects will be analyzed: liver serum biochemistry, serum and urine bile acids metabolites, transient elastography and health related quality of life.
Read the detailed description
Background: Primary biliary cirrhosis is a chronic cholestatic liver disorder which may lead to end stage liver disease causing death or requiring liver transplantation. Additionally, a significant proportion of patients suffers from complications related to impaired bile secretion such as intractable pruritus, chronic fatigue, osteoporosis or lipid disturbance. They all have a significant consequence for patients well being, quality of life and economical aspects of health care systems. Pathogenesis of PBC remains to be fully elucidated. Recent studies show,that chronic liver diseases are associated with an acquired deficiency of S-adenosyl-L-methionine synthetase, an enzyme responsible for the synthesis of SAMe from methionine. SAMe initiates two very important protective metabolic pathways: transmethylation and transsulphuration. As a result of the later, glutathione, taurine and sulphate group are synthesized. Thus SAMe deficiency is associated with impaired detoxification and hepatoprotection and exacerbate liver injury. Supplementation with SAMe has proven useful in alcoholic liver disease, obstetric cholestasis and elimination of hepatitis C virus (HCV). The investigators' studies on experimental models where cholestasis was induced in vitro with lithocholic acid and 17-beta estradiol glucuronide showed that supplementation with SAMe exerts a significant anticholestatic effect. Interestingly, simultaneous administration of SAMe and ursodeoxycholic acid (UDCA) exerts an additive effect.
Methods: The study group will include 20 patients PBC diagnosed with EASL criteria, who have been already treated with UDCA. They will receive UDCA in the dose of 13 - 15mg/kg bw plus SAMe in the dose of 1600 mg bd over the period of 6 months.
The key aim of the project is to analyze the effect of SAMe on the health related quality of life and liver biochemistry. Blood and urine samples (from 24hr urine collection) will be collected for liver biochemistry and metabolites of bile acids. Additionally transient elastography will be performed before and after 6 months SAMe treatment.
- Conditions
- Primary Biliary Cirrhosis
- Being tested
- S-adenosyl-L-methionine
- Keywords
- liver injury, detoxification, S-adenosyl-L-methionine, quality of life
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-adenosyl-L-methionineDietary supplement
Patients will be treated with S-adenosyl-L-methionine, tablets 800 mg twice a day (daily dosage 1600 mg) for six months
| Study group | Role | What they receive |
|---|---|---|
| S-adenosyl-L-methionine | Experimental | Patients with primary biliary cirrhosis will be treated with S-adenosyl-L-methionine, tablets 800 mg twice a day (daily dosage 1600 mg) for six months Receives: Dietary Supplement: S-adenosyl-L-methionine |
What is being measured
The primary outcome is the main question the study is designed to answer.
PBC-40 questionnaire
Questionnaire consists 40 questions in 5 domains: Cognition, Itch, Fatigue, Social-Emotional and Other Symptoms, marked with a five-point scale (1=never to 5=always), with higher scores denoting greater symptoms impact and poorer quality of life. The possible range of each domain were: Other Symptoms domain 7-35, Itch 3-15, Fatigue 11-55, Cognitive 6-30, Social and Emotional 13-65 points.
Measured: 6 months
Secondary outcomes (3)
Liver fibrosis measured by transient elastography
To analyse the influence of SAMe treatment on liver stiffness
Measured: 6 months
Number of participants with abnormal laboratory values (liver biochemistry)
To analyse the influence of SAMe treatment on liver function parameters
Measured: 6 months
Number of participants with changes in bile acids pool
To analyse the influence of SAMe treatment on 17 bile acids metabolites in serum and urine
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2015 (estimated)
- Study startNov 2015
- Primary completionFeb 2017
- Study completionMar 2017
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 Primary Biliary CirrhosisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pomeranian Medical University Szczecin
- Sponsor type
- University, hospital or other
- Collaborators
- Laval University
- Responsible party
- Principal investigator, Wunsch Ewa, Pomeranian Medical University Szczecin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02557360
- Sponsor's protocol ID
- 2011/02/A/NZ5/00321
- Status last verified
- Mar 2017
- First submitted
- 21 Sep 2015
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Wunsch E, Raszeja-Wyszomirska J, Barbier O, Milkiewicz M, Krawczyk M, Milkiewicz P. Effect of S-adenosyl-L-methionine on liver biochemistry and quality of life in patients with primary biliary cholangitis treated with ursodeoxycholic acid. A prospective, open label pilot study. J Gastrointestin Liver Dis. 2018 Sep;27(3):273-279. doi: 10.15403/jgld.2014.1121.273.icz.
PubMed 30240471
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis
- ClinicalTrials.gov ID
- NCT02557360
- Acronym / sponsor ID
- 2011/02/A/NZ5/00321
- Conditions
- Primary Biliary Cirrhosis
- Keywords
- liver injury, detoxification, S-adenosyl-L-methionine, quality of life
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Pomeranian Medical University SzczecinUniversity, hospital or other
- Collaborators
- Laval University
- Study start
- Nov 2015
- Primary completion
- Feb 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 23 Sep 2015 (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.
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder which may lead to several symptoms such as intractable pruritus or chronic fatigue, significantly impairing patients quality of life. Recent studies show, that chronic liver diseases are associated with an acquired deficiency of S-adenosyl-L-methionine (SAMe) synthetase, responsible for the synthesis of SAMe from methionine. SAMe deficiency is associated with impaired detoxification and hepatoprotection and exacerbate liver injury. Supplementation with SAMe has proven useful in several liver diseases.
The study group will include 20 patients with PBC diagnosed with European Association for the Study of the Liver (EASL) criteria, who have been already treated with ursodeoxycholic acid (UDCA). They will receive SAMe in the dose of 1600 mg bd over the period of 6 months. Both clinical and laboratory aspects will be analyzed: liver serum biochemistry, serum and urine bile acids metabolites, transient elastography and health related quality of life.
Detailed description
Background: Primary biliary cirrhosis is a chronic cholestatic liver disorder which may lead to end stage liver disease causing death or requiring liver transplantation. Additionally, a significant proportion of patients suffers from complications related to impaired bile secretion such as intractable pruritus, chronic fatigue, osteoporosis or lipid disturbance. They all have a significant consequence for patients well being, quality of life and economical aspects of health care systems. Pathogenesis of PBC remains to be fully elucidated. Recent studies show,that chronic liver diseases are associated with an acquired deficiency of S-adenosyl-L-methionine synthetase, an enzyme responsible for the synthesis of SAMe from methionine. SAMe initiates two very important protective metabolic pathways: transmethylation and transsulphuration. As a result of the later, glutathione, taurine and sulphate group are synthesized. Thus SAMe deficiency is associated with impaired detoxification and hepatoprotection and exacerbate liver injury. Supplementation with SAMe has proven useful in alcoholic liver disease, obstetric cholestasis and elimination of hepatitis C virus (HCV). The investigators' studies on experimental models where cholestasis was induced in vitro with lithocholic acid and 17-beta estradiol glucuronide showed that supplementation with SAMe exerts a significant anticholestatic effect. Interestingly, simultaneous administration of SAMe and ursodeoxycholic acid (UDCA) exerts an additive effect.
Methods: The study group will include 20 patients PBC diagnosed with EASL criteria, who have been already treated with UDCA. They will receive UDCA in the dose of 13 - 15mg/kg bw plus SAMe in the dose of 1600 mg bd over the period of 6 months.
The key aim of the project is to analyze the effect of SAMe on the health related quality of life and liver biochemistry. Blood and urine samples (from 24hr urine collection) will be collected for liver biochemistry and metabolites of bile acids. Additionally transient elastography will be performed before and after 6 months SAMe treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| S-adenosyl-L-methionine | Experimental | Dietary Supplement: S-adenosyl-L-methioninePatients with primary biliary cirrhosis will be treated with S-adenosyl-L-methionine, tablets 800 mg twice a day (daily dosage 1600 mg) for six months |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- primary biliary cirrhosis diagnosed with EASL criteria;
- treatment with UDCA at least 3 months.
Key exclusion criteria (4 listed)
- overlap syndromes (i.e. autoimmune hepatitis), viral hepatitis;
- decompensated liver cirrhosis (Child-Pugh class B-C);
- other diseases that can affect quality of life and mood: decompensated diabetes mellitus, renal insufficiency requiring dialyses, malignancy, heart failure ≥ New York Heart Association (NYHA) II, rheumatoid arthritis, asthma, mood disorders, depression;
- treatment with: steroids, statins, rifampicin, antidepressants.
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-L-methioninePatients will be treated with S-adenosyl-L-methionine, tablets 800 mg twice a day (daily dosage 1600 mg) for six months | Dietary supplement | S-adenosyl-L-methionine |
Primary outcome
PBC-40 questionnaire
Time frame: 6 months
Questionnaire consists 40 questions in 5 domains: Cognition, Itch, Fatigue, Social-Emotional and Other Symptoms, marked with a five-point scale (1=never to 5=always), with higher scores denoting greater symptoms impact and poorer quality of life. The possible range of each domain were: Other Symptoms domain 7-35, Itch 3-15, Fatigue 11-55, Cognitive 6-30, Social and Emotional 13-65 points.
3 secondary outcomes
Liver fibrosis measured by transient elastography
Time frame: 6 months
Number of participants with abnormal laboratory values (liver biochemistry)
Time frame: 6 months
Number of participants with changes in bile acids pool
Time frame: 6 months
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 28 Mar 2017.
- Derived from this study: PubMed 30240471Wunsch E, Raszeja-Wyszomirska J, Barbier O, Milkiewicz M, Krawczyk M, Milkiewicz P. Effect of S-adenosyl-L-methionine on liver biochemistry and quality of life in patients with primary biliary cholangitis treated with ursodeoxycholic acid. A prospective, open label pilot study. J Gastrointestin Liver Dis. 2018 Sep;27(3):273-279. doi: 10.15403/jgld.2014.1121.273.icz.
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing S-adenosyl-L-methionine in people with Primary Biliary Cirrhosis, run by Pomeranian Medical University Szczecin at 2 sites in Poland.
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 4 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 28 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
PBC-40 questionnaire (time frame: 6 months). 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 NCT02557360, 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 28 Mar 2017.