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

Phase 4

Completed

• Conditions: Primary Biliary Cirrhosis
• Interventions: Dietary Supplement: S-adenosyl-L-methionine

• Registration Number: NCT02557360
• Lead Sponsor: Pomeranian Medical University Szczecin

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 Timeline

• Study First Submitted: 2015-09-21
• Study First Submitted QC: 2015-09-21
• Study First Posted: 2015-09-23
• Study Start: 2015-11
• Primary Completion: 2017-02
• Status Verified: 2017-03
• Study Completion: 2017-03
• Last Update Submitted: 2017-03-27
• Last Update Posted: 2017-03-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
S-adenosyl-L-methionine	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

Primary Outcome Measures

Name	Time	Method
PBC-40 questionnaire	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

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

Trial Locations

Locations (2)

Wunsch; 🇵🇱 Szczecin, Poland

Milkiewicz; 🇵🇱 Warsaw, Poland