Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis

• ClinicalTrials.gov Identifier: NCT02557360
• Recruitment Status: Completed
• First Posted: September 23, 2015
• Last Update Posted: March 28, 2017
• Sponsor: Pomeranian Medical University Szczecin
• Collaborator: Laval University
• Information provided by (Responsible Party): Wunsch Ewa, Pomeranian Medical University Szczecin

Tracking Information

• First Submitted Date: September 21, 2015
• First Posted Date: September 23, 2015
• Last Update Posted Date: March 28, 2017
• Study Start Date: November 2015
• Actual Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 21, 2015)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 22, 2015)

• Liver fibrosis measured by transient elastography [ Time Frame: 6 months ]
  To analyse the influence of SAMe treatment on liver stiffness
• Number of participants with abnormal laboratory values (liver biochemistry) [ Time Frame: 6 months ]
  To analyse the influence of SAMe treatment on liver function parameters
• Number of participants with changes in bile acids pool [ Time Frame: 6 months ]
  To analyse the influence of SAMe treatment on 17 bile acids metabolites in serum and urine

Original Secondary Outcome Measures (submitted: September 21, 2015)

• liver fibrosis measured by transient elastography [ Time Frame: 6 months ]
  To analyse the influence of SAMe treatment on liver stiffness
• liver biochemistry: alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin [ Time Frame: 6 months ]
  To analyse the influence of SAMe treatment on liver function parameters
• bile acids metabolites [ Time Frame: 6 months ]
  To analyse the influence of SAMe treatment on 17 bile acids metabolites in serum and urine

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis
• Official Title: Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis

Brief 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. 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Primary Biliary Cirrhosis

Intervention

Dietary Supplement: S-adenosyl-L-methionine

Patients will be treated with S-adenosyl-L-methionine, tablets 800 mg twice a day (daily dosage 1600 mg) for six months

Study Arms

Experimental: S-adenosyl-L-methionine

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

Intervention: Dietary Supplement: S-adenosyl-L-methionine

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 27, 2017): 24
• Original Estimated Enrollment (submitted: September 21, 2015): 20
• Actual Study Completion Date: March 2017
• Actual Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• primary biliary cirrhosis diagnosed with EASL criteria;
• treatment with UDCA at least 3 months.

Exclusion Criteria:

• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Poland

Administrative Information

• NCT Number: NCT02557360
• Other Study ID Numbers: 2011/02/A/NZ5/00321
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Wunsch Ewa, Pomeranian Medical University Szczecin
• Original Responsible Party: Same as current
• Current Study Sponsor: Pomeranian Medical University Szczecin
• Original Study Sponsor: Same as current
• Collaborators: Laval University
• Investigators: Not Provided
• PRS Account: Pomeranian Medical University Szczecin
• Verification Date: March 2017