xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06026865</url>
    </required_header>
    <id_info>
      <org_study_id>2020/39/O/NZ5/03594</org_study_id>
      <nct_id>NCT06026865</nct_id>
    </id_info>
    <brief_title>S-adenosylmethionine (SAMe) in Patients With Primary Sclerosing Cholangitis (PSC)</brief_title>
    <official_title>Clinical Effect and Molecular Mechanisms of Action of S-adenosylmethionine (SAMe) in Patients With Primary Sclerosing Cholangitis (PSC)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Medical University of Warsaw</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Science Centre, Poland</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Medical University of Warsaw</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this study is to investigate clinical effects (liver biochemistries,&#xD;
        health-related quality of life, liver stiffness) and underlying mechanisms of&#xD;
        hepatoprotection of S-adenosylmethionine in patients with primary sclerosing cholangitis. The&#xD;
        study will be performed in a randomized and placebo-controlled fashion.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study is designed as a randomised, double-blind, placebo-controlled trial.&#xD;
  &#xD;
        Eighty participants will be randomized in 1:1 ratio to one of two arms of the study:&#xD;
        Intervention or Placebo. Participants in Intervention Group will be treated with&#xD;
        S-adenosyl-L-methionine 1200 mg/daily in tablets in two divided doses (800mg in the morning&#xD;
        and 400mg midday) over the period of 6 months. Patients in Placebo Group will receive a&#xD;
        placebo of identical appearance, smell and taste, with the same schedule.&#xD;
  &#xD;
        Participants will be monitored in out-patient clinic at baseline, interim visits at weeks: 4,&#xD;
        12, end of treatment at 24 weeks and follow-up visit after 4-6 weeks wash-out period.&#xD;
        Treatment adherence, adverse events, serum biochemistry and health related quality of life&#xD;
        will be assessed at each visit. Liver fibrosis will be measured with transient elastography&#xD;
        at baseline and at the end of treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 1, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in liver biochemistries</measure>
      <time_frame>6 months</time_frame>
      <description>Change in levels of liver enzymes (Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyltransferase, Alkaline Phosphatase)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Health-related Quality of Life</measure>
      <time_frame>6 months</time_frame>
      <description>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).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in PSC-related Quality of Life</measure>
      <time_frame>6 months</time_frame>
      <description>Change in severity of chronic fatigue and other aspects of health-related quality of life assessed by questionnaire PBC-40.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Quality of Life</measure>
      <time_frame>6 months</time_frame>
      <description>Change in severity of generalized anxiety disorder assessed by questionnaire GAD-7 (General Anxiety Disorder-7).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in pruritus severity</measure>
      <time_frame>6 months</time_frame>
      <description>Change in pruritus severity on the Visual Analogue Scale (VAS) - 0 (no pruritus) to 10 (worst pruritus).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in liver stiffness</measure>
      <time_frame>6 months</time_frame>
      <description>Change in liver stiffness on liver elastography (measured in kPa)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Molecular assesment of hepatoprotective properties of SAMe</measure>
      <time_frame>6 months</time_frame>
      <description>Assessment of changes in antioxidant defence system (assessed as plasma MDA, SOD2, FGF-19, TNF-α, IL6, IL10, TGFβ, INFγ, homocysteine concentrations).</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Primary Sclerosing Cholangitis (PSC)</condition>
    <arm_group>
      <arm_group_label>S-adenosylmethionine (SAMe)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>S-Adenosyl-L-methionine (SAMe)</intervention_name>
      <description>S-adenosyl-L-methionine 1200 mg/daily as 2400mg S-Adenosyl-L-methionine disulfate tosylate</description>
      <arm_group_label>S-adenosylmethionine (SAMe)</arm_group_label>
      <other_name>S-adenosylmethionine</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo of identical appearance, smell and taste, with the same schedule.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  primary sclerosing cholangitis fulfilling EASL criteria;&#xD;
  &#xD;
            -  age: 18 - 75 years;&#xD;
  &#xD;
            -  treatment with ursodeoxycholic acid (UDCA) in a dose of 13-15mg/kg b.w. for at least 6&#xD;
               months.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  inability to give informed consent;&#xD;
  &#xD;
            -  patients with other forms of chronic liver diseases;&#xD;
  &#xD;
            -  decompensated liver cirrhosis (Child-Pugh class B-C);&#xD;
  &#xD;
            -  patients with PSC who underwent stenting of their biliary tree within 6 months;&#xD;
  &#xD;
            -  other diseases or states that can affect quality of life and mood: decompensated&#xD;
               diabetes mellitus, renal insufficiency requiring dialyses, malignancy, heart failure ≥&#xD;
               New York Heart Association (NYHA) II, organ transplantation, known HIV infection,&#xD;
               rheumatoid arthritis, asthma, psychiatric disorders;&#xD;
  &#xD;
            -  treatment with: steroids, statins, rifampicin, antidepressants;&#xD;
  &#xD;
            -  pregnant or breastfeeding women;&#xD;
  &#xD;
            -  history of hypersensitivity reactions to S-adenosylmethionine;&#xD;
  &#xD;
            -  any other condition, which in the opinion of the investigators would impede the&#xD;
               patient's participation or compliance in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Piotr Milkiewicz, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Department of Hepatology, Transplantology and Internal Medicine, Medical University of Warsaw</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Emil Bik, MD</last_name>
      <phone>+48 22 599 16 62</phone>
      <email>emil.bik@uckwum.pl</email>
    </overall_contact>
    <location>
      <facility>
        <name>Department of Hepatology, Transplantology and Internal Medicine, Medical University of Warsaw</name>
        <address>
          <city>Warsaw</city>
          <country>Poland</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Emil Bik, MD</last_name>
        <phone>+48 22 599 16 62</phone>
        <email>emil.bik@uckwum.pl</email>
      </contact>
    </location>
    <location_countries>
      <country>Poland</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 9, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>PSC</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cholangitis</mesh_term>
      <mesh_term>Cholangitis, Sclerosing</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06026865
  org study id: 2020/39/O/NZ5/03594
  nct id: NCT06026865
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: Change in liver biochemistries
  time frame: 6 months
  description: Change in levels of liver enzymes (Aspartate Transaminase, Alanine Transaminase, Gamma-glutamyltransferase, Alkaline Phosphatase)
  measure: Change in Health-related Quality of Life
  time frame: 6 months
  description: 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).
  measure: Change in PSC-related Quality of Life
  time frame: 6 months
  description: Change in severity of chronic fatigue and other aspects of health-related quality of life assessed by questionnaire PBC-40.
  measure: Change in Quality of Life
  time frame: 6 months
  description: Change in severity of generalized anxiety disorder assessed by questionnaire GAD-7 (General Anxiety Disorder-7).
  measure: Change in pruritus severity
  time frame: 6 months
  description: Change in pruritus severity on the Visual Analogue Scale (VAS) - 0 (no pruritus) to 10 (worst pruritus).
  measure: Change in liver stiffness
  time frame: 6 months
  description: Change in liver stiffness on liver elastography (measured in kPa)
  measure: Molecular assesment of hepatoprotective properties of SAMe
  time frame: 6 months
  description: Assessment of changes in antioxidant defence system (assessed as plasma MDA, SOD2, FGF-19, TNF-α, IL6, IL10, TGFβ, INFγ, homocysteine concentrations).
  arm group label: S-adenosylmethionine (SAMe)
  arm group type: Experimental
  description: 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.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: 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.
  intervention type: Dietary Supplement
  intervention name: S-Adenosyl-L-methionine (SAMe)
  description: S-adenosyl-L-methionine 1200 mg/daily as 2400mg S-Adenosyl-L-methionine disulfate tosylate
  arm group label: S-adenosylmethionine (SAMe)
  other name: S-adenosylmethionine
  intervention type: Other
  intervention name: Placebo
  description: Placebo of identical appearance, smell and taste, with the same schedule.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Piotr Milkiewicz, MD, PhD
  role: Principal Investigator
  affiliation: Department of Hepatology, Transplantology and Internal Medicine, Medical University of Warsaw
  last name: Emil Bik, MD
  phone: +48 22 599 16 62
  email: emil.bik@uckwum.pl
  facility: 
  status: Recruiting
  contact: 
  country: Poland
  responsible party type: Sponsor
  mesh term: Cholangitis
  mesh term: Cholangitis, Sclerosing
  sharing ipd: No