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

This study has been completed.
Sponsor:
Collaborator:
Laval University
Information provided by (Responsible Party):
Wunsch Ewa, Pomeranian Medical University Szczecin
ClinicalTrials.gov Identifier:
NCT02557360
First received: September 21, 2015
Last updated: March 27, 2017
Last verified: March 2017
  Purpose

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.


Condition Intervention Phase
Primary Biliary Cirrhosis
Dietary Supplement: S-adenosyl-L-methionine
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by Pomeranian Medical University Szczecin:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 24
Study Start Date: November 2015
Study Completion Date: March 2017
Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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

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.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02557360

Locations
Poland
Wunsch
Szczecin, Poland
Milkiewicz
Warsaw, Poland
Sponsors and Collaborators
Pomeranian Medical University Szczecin
Laval University
  More Information

Responsible Party: Wunsch Ewa, MD, Pomeranian Medical University Szczecin
ClinicalTrials.gov Identifier: NCT02557360     History of Changes
Other Study ID Numbers: 2011/02/A/NZ5/00321
Study First Received: September 21, 2015
Last Updated: March 27, 2017

Keywords provided by Pomeranian Medical University Szczecin:
liver injury
detoxification
S-adenosyl-L-methionine
quality of life

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases

ClinicalTrials.gov processed this record on March 28, 2017