<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/NCT02231333</url>
  </required_header>
  <id_info>
    <org_study_id>ILBS-NASH-01</org_study_id>
    <nct_id>NCT02231333</nct_id>
  </id_info>
  <brief_title>The Efficacy of S-adenosyl Methionine (SAMe) Versus Pentoxiphylline in Patients With Non-alcoholic Steatohepatitis With Fibrosis</brief_title>
  <official_title>A Randomized Controlled Trial to Study the Efficacy of S-adenosyl Methionine (SAMe) Versus Pentoxiphylline in Patients With Non-alcoholic Steatohepatitis With Fibrosis.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Liver and Biliary Sciences, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Liver and Biliary Sciences, India</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Nonalcoholic fatty liver disease is one the most commonly encountered conditions in a daily&#xD;
      outpatient Hepatology clinic. Secondly our country is the diabetic capital of the world and&#xD;
      so the incidence of NAFLD (Non Alcoholic Fatty Liver Disease) is expected to rise in the&#xD;
      future. It is a spectrum of hepatic pathology, ranging from simple steatosis,&#xD;
      steatohepatitis, to cirrhosis. Nonalcoholic steatohepatitis (NASH) is a more advanced form of&#xD;
      disease where steatosis is accompanied by hepatocyte injury as well as infiltration of&#xD;
      inflammatory cells. Approximately 10-20% of patients with NASH may progress to cirrhosis.&#xD;
      NASH is felt to be a major etiology of cryptogenic cirrhosis. Around 6230 human studies out&#xD;
      of which 49 RCTs have been done till date to define the appropriate treatment of nonalcoholic&#xD;
      steatohepatitis. However, still a controversy and no recommended treatment available till&#xD;
      date. Recently published PIVENS trial has shown that Vitamin E has proven benefit in NASH.&#xD;
      Other trials have also shown that pentoxiphylline has shown benefit in the form of&#xD;
      histological improvement and biochemical improvement in the form of liver enzymes. Role of&#xD;
      SAMe has been studied in alcoholic liver disease and showed to improve in both biochemical&#xD;
      and histological features. However the usefulness of SAMe in NAFLD is not known till now.&#xD;
      Hence this study has been designed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2013</start_date>
  <completion_date type="Actual">July 31, 2015</completion_date>
  <primary_completion_date type="Actual">July 31, 2015</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Biochemical improvement in the form of AST/ALT</measure>
    <time_frame>1 Years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Improvement in LSM (Liver Stiffness Measurement) &amp; CAP (Controlled Attenuation Parameter)</measure>
    <time_frame>1 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Metabolic response in form of anthropometry.</measure>
    <time_frame>1 Years</time_frame>
    <description>metabolic response in form of anthropometry (BMI, waist circumference).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting lipid profiles</measure>
    <time_frame>1 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in uric acid levels</measure>
    <time_frame>1 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in pro- inflammatory cytokines</measure>
    <time_frame>1 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histological outcome in the form of improvement or non- progression in hepatocyte injury and fibrosis.</measure>
    <time_frame>1 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Non-alcoholic Steatohepatitis</condition>
  <arm_group>
    <arm_group_label>S-adenosylmethionine (SAMe)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>pentoxiphylline (PTX)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>S-adenosylmethionine (SAMe)</intervention_name>
    <arm_group_label>S-adenosylmethionine (SAMe)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pentoxiphylline (PTX)</intervention_name>
    <arm_group_label>pentoxiphylline (PTX)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 to 70 years&#xD;
&#xD;
          -  Persistently abnormal ALT &gt;1.2 times upper limit of normal&#xD;
&#xD;
          -  Histological evidence of NASH (Non alcoholic Steatohepatitis) on liver biopsy. The&#xD;
             minimal criteria for diagnosis of NASH included the presence of lobular inflammation&#xD;
             and fibrosis up to stage 3 as per Burnt stating.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Alcohol intake of more than 40gm / week with features suggestive chronic liver disease&#xD;
             .&#xD;
&#xD;
          -  Other known cause of chronic liver disease like Hepatitis B,C, autoimmune liver&#xD;
             disease, Wilson's disease, alpha 1 antitrypsin deficiency and hemochromatosis, primary&#xD;
             biliary cirrhosis, PSC (Primary Sclerosis Cholangitis).&#xD;
&#xD;
          -  Patient on Medication like estrogens, amiodarone, MTx, tamoxifen, ATT (Antitubercular&#xD;
             Treatment)&#xD;
&#xD;
          -  Pregnancy or lactation&#xD;
&#xD;
          -  Hypersensitivity to methylxanthines (e.g., caffeine, theophylline,)&#xD;
&#xD;
          -  Recent retinal/cerebral hemorrhage&#xD;
&#xD;
          -  Acute myocardial infarction or severe cardiac arrhythmias.&#xD;
&#xD;
          -  Impaired renal function.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr Devaraja R, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Liver and Biliary Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Liver &amp; Biliary Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110070</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>August 30, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>October 25, 2019</last_update_submitted>
  <last_update_submitted_qc>October 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pentoxifylline</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT02231333
org study id: ILBS-NASH-01
nct id: NCT02231333
lead sponsor: 
has dmc: No
Nonalcoholic fatty liver disease is one the most commonly encountered conditions in a daily
      outpatient Hepatology clinic. Secondly our country is the diabetic capital of the world and
      so the incidence of NAFLD (Non Alcoholic Fatty Liver Disease) is expected to rise in the
      future. It is a spectrum of hepatic pathology, ranging from simple steatosis,
      steatohepatitis, to cirrhosis. Nonalcoholic steatohepatitis (NASH) is a more advanced form of
      disease where steatosis is accompanied by hepatocyte injury as well as infiltration of
      inflammatory cells. Approximately 10-20% of patients with NASH may progress to cirrhosis.
      NASH is felt to be a major etiology of cryptogenic cirrhosis. Around 6230 human studies out
      of which 49 RCTs have been done till date to define the appropriate treatment of nonalcoholic
      steatohepatitis. However, still a controversy and no recommended treatment available till
      date. Recently published PIVENS trial has shown that Vitamin E has proven benefit in NASH.
      Other trials have also shown that pentoxiphylline has shown benefit in the form of
      histological improvement and biochemical improvement in the form of liver enzymes. Role of
      SAMe has been studied in alcoholic liver disease and showed to improve in both biochemical
      and histological features. However the usefulness of SAMe in NAFLD is not known till now.
      Hence this study has been designed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Biochemical improvement in the form of AST/ALT
time frame: 1 Years
measure: Improvement in LSM (Liver Stiffness Measurement) & CAP (Controlled Attenuation Parameter)
time frame: 1 years
measure: Metabolic response in form of anthropometry.
time frame: 1 Years
description: metabolic response in form of anthropometry (BMI, waist circumference).
measure: Fasting lipid profiles
time frame: 1 Years
measure: Reduction in uric acid levels
time frame: 1 Years
measure: Reduction in pro- inflammatory cytokines
time frame: 1 Years
measure: Histological outcome in the form of improvement or non- progression in hepatocyte injury and fibrosis.
time frame: 1 years
arm group label: S-adenosylmethionine (SAMe)
arm group type: Experimental
arm group label: pentoxiphylline (PTX)
arm group type: Active Comparator
intervention type: Drug
intervention name: S-adenosylmethionine (SAMe)
arm group label: S-adenosylmethionine (SAMe)
intervention type: Drug
intervention name: pentoxiphylline (PTX)
arm group label: pentoxiphylline (PTX)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Dr Devaraja R, MD
role: Principal Investigator
affiliation: Institute of Liver and Biliary Sciences
facility: 
country: India
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
mesh term: Pentoxifylline