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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02557360
Recruitment Status : Completed
First Posted : September 23, 2015
Last Update Posted : March 28, 2017
Sponsor:
Collaborator:
Laval University
Information provided by (Responsible Party):
Wunsch Ewa, Pomeranian Medical University Szczecin

Tracking Information
First Submitted Date  ICMJE September 21, 2015
First Posted Date  ICMJE September 23, 2015
Last Update Posted Date March 28, 2017
Study Start Date  ICMJE November 2015
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE Effectiveness of S-adenosyl-L-methionine in Patients With Primary Biliary Cirrhosis
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Primary Biliary Cirrhosis
Intervention  ICMJE 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  ICMJE 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 27, 2017)
24
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2015)
20
Actual Study Completion Date  ICMJE March 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02557360
Other Study ID Numbers  ICMJE 2011/02/A/NZ5/00321
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Wunsch Ewa, Pomeranian Medical University Szczecin
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Pomeranian Medical University Szczecin
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Laval University
Investigators  ICMJE Not Provided
PRS Account Pomeranian Medical University Szczecin
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP