S-adenosylmethionine (SAMe) in Patients With Primary Sclerosing Cholangitis (PSC)

Clinical Effect and Molecular Mechanisms of Action of S-adenosylmethionine (SAMe) in Patients With Primary Sclerosing Cholangitis (PSC)

The aim of this study is to investigate clinical effects (liver biochemistries, health-related quality of life, liver stiffness) and underlying mechanisms of hepatoprotection of S-adenosylmethionine in patients with primary sclerosing cholangitis. The study will be performed in a randomized and placebo-controlled fashion.

Study Overview

• Status: Active, not recruiting
• Conditions: Primary Sclerosing Cholangitis (PSC)
• Intervention / Treatment: Dietary supplement: S-Adenosyl-L-methionine (SAMe); Other: Placebo

Detailed Description

The study is designed as a randomised, double-blind, placebo-controlled trial.

Eighty participants will be randomized in 1:1 ratio to one of two arms of the study: Intervention or Placebo. Participants in Intervention Group will be treated with S-adenosyl-L-methionine 1200 mg/daily in tablets in two divided doses (800mg in the morning and 400mg midday) over the period of 6 months. Patients in Placebo Group will receive a placebo of identical appearance, smell and taste, with the same schedule.

Participants will be monitored in out-patient clinic at baseline, interim visits at weeks: 4, 12, end of treatment at 24 weeks and follow-up visit after 4-6 weeks wash-out period. Treatment adherence, adverse events, serum biochemistry and health related quality of life will be assessed at each visit. Liver fibrosis will be measured with transient elastography at baseline and at the end of treatment.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland
    • Department of Hepatology, Transplantology and Internal Medicine, Medical University of Warsaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• primary sclerosing cholangitis fulfilling EASL criteria;
• age: 18 - 75 years;
• treatment with ursodeoxycholic acid (UDCA) in a dose of 13-15mg/kg b.w. for at least 6 months.

Exclusion Criteria:

• inability to give informed consent;
• patients with other forms of chronic liver diseases;
• decompensated liver cirrhosis (Child-Pugh class B-C);
• patients with PSC who underwent stenting of their biliary tree within 6 months;
• other diseases or states that can affect quality of life and mood: decompensated diabetes mellitus, renal insufficiency requiring dialyses, malignancy, heart failure ≥ New York Heart Association (NYHA) II, organ transplantation, known HIV infection, rheumatoid arthritis, asthma, psychiatric disorders;
• treatment with: steroids, statins, rifampicin, antidepressants;
• pregnant or breastfeeding women;
• history of hypersensitivity reactions to S-adenosylmethionine;
• any other condition, which in the opinion of the investigators would impede the patient's participation or compliance in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-adenosylmethionine (SAMe); Participants randomized to SAMe Group will receive S-adenosyl-L-methionine 1200 mg/daily (as 2400mg SAMe disulfate tosylate) in tablets in two divided doses (800mg in the morning and 400mg midday) over the period of 6 months. In addition, patients will receive standard treatment with ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg b.w.	Dietary supplement: S-Adenosyl-L-methionine (SAMe); S-adenosyl-L-methionine 1200 mg/daily as 2400mg S-Adenosyl-L-methionine disulfate tosylate; Other Names: S-adenosylmethionine
Placebo Comparator: Placebo; Patients in Placebo Group will receive a placebo of identical appearance, smell and taste, with the same schedule. In addition, patients will receive standard treatment with ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg.In addition, patients will receive standard treatment with ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg b.w.	Other: Placebo; Placebo of identical appearance, smell and taste, with the same schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver biochemistries	Change in levels of liver enzymes (Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyltransferase, Alkaline Phosphatase)	6 months
Change in Health-related Quality of Life	Change in severity of chronic fatigue and other aspects of health-related quality of life assessed by questionnaire SF-36 (36-Item Short Form Survey).	6 months
Change in PSC-related Quality of Life	Change in severity of chronic fatigue and other aspects of health-related quality of life assessed by questionnaire PBC-40.	6 months
Change in Quality of Life	Change in severity of generalized anxiety disorder assessed by questionnaire GAD-7 (General Anxiety Disorder-7).	6 months
Change in pruritus severity	Change in pruritus severity on the Visual Analogue Scale (VAS) - 0 (no pruritus) to 10 (worst pruritus).	6 months
Change in liver stiffness	Change in liver stiffness on liver elastography (measured in kPa)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular assesment of hepatoprotective properties of SAMe	Assessment of changes in antioxidant defence system (assessed as plasma MDA, SOD2, FGF-19, TNF-α, IL6, IL10, TGFβ, INFγ, homocysteine concentrations).	6 months

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: National Science Centre, Poland
• Investigators: Principal Investigator: Piotr Milkiewicz, MD, PhD, Department of Hepatology, Transplantology and Internal Medicine, Medical University of Warsaw

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: June 9, 2023
• First Submitted That Met QC Criteria: September 4, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 30, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: PSC
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: 2020/39/O/NZ5/03594

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No