<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/NCT01680250</url>
  </required_header>
  <id_info>
    <org_study_id>SILVER</org_study_id>
    <nct_id>NCT01680250</nct_id>
  </id_info>
  <brief_title>Sirolimus for Massive Polycystic Liver</brief_title>
  <acronym>SILVER</acronym>
  <official_title>An Open-label, Prospective Clinical Trial to Evaluate the Effectiveness and Safety of Sirolimus to Reduce Cyst Growth in ADPKD Patients With Massive Polycystic Liver</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Wyeth is now a wholly owned subsidiary of Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effectiveness and safety of Sirolimus in&#xD;
      reducing liver volume in autosomal dominant polycystic kidney disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of end&#xD;
      stage renal disease (ESRD), affecting an estimated 0.2% of population. Of ADPKD patients, 58%&#xD;
      in 15-24 year, 85% in 25-34 year, and 94% in 35-46 year olds suffer from polycystic liver in&#xD;
      addition to polycystic kidneys. Several anti-proliferative drugs have been used in clinical&#xD;
      trials to stop cyst growth both in liver and kidneys. Among them, octreotide and sirolimus&#xD;
      have been shown to be one of the most promising drugs to reduce cyst volume. Sirolimus&#xD;
      already has been used as one of the most potential oral immunosuppressants. Moreover, the&#xD;
      serum trough level is quite easy to measure. Sirolimus is the mTOR inhibitor that has been&#xD;
      proven to be effective in reducing cyst growth both in animal models. However, its efficacy&#xD;
      and safety is not well proven in previous studies. This is a open-label, prospective study to&#xD;
      evaluate the effectiveness and safety of Sirolimus to reduce cyst growth in ADPKD patients&#xD;
      with massive polycystic liver.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2011</start_date>
  <completion_date type="Anticipated">August 2015</completion_date>
  <primary_completion_date type="Anticipated">September 2014</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total liver volume</measure>
    <time_frame>12 months</time_frame>
    <description>Change in total liver volume</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total liver volume</measure>
    <time_frame>24 months</time_frame>
    <description>Change in total liver volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total kidney volume</measure>
    <time_frame>12 month</time_frame>
    <description>Change in total kidney volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimated glomerular filtration rate</measure>
    <time_frame>12 month</time_frame>
    <description>Change in estimated glomerular filtration rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary biomarker</measure>
    <time_frame>12 month</time_frame>
    <description>Urinary biomarker level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total kidney volume</measure>
    <time_frame>24 month</time_frame>
    <description>Change in total kidney volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimated glomerular filtration rate</measure>
    <time_frame>24 month</time_frame>
    <description>Change in estimated glomerular filtration rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urinary biomarker</measure>
    <time_frame>24 month</time_frame>
    <description>Urinary biomarker level</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Abdominal pain</measure>
    <time_frame>12month</time_frame>
    <description>Abdominal pain quantified by Visual Analog Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Abdominal pain</measure>
    <time_frame>24 month</time_frame>
    <description>Abdominal pain quantified by Visual Analog Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Infection</measure>
    <time_frame>24 month</time_frame>
    <description>Incidence of infection event during study time</description>
  </other_outcome>
  <other_outcome>
    <measure>Hospitalization</measure>
    <time_frame>24 month</time_frame>
    <description>Incidence of hospitalization due to adverse events during study time</description>
  </other_outcome>
  <other_outcome>
    <measure>Drop out</measure>
    <time_frame>24 month</time_frame>
    <description>Incidence of discontinuation of study drug due to serious adverse events during study time</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Polycystic Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Sirolimus</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sirolimus administration group starting dose: 2mg/day target trough level: 4-10 ng/dL</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Sirolimus administration for 12 months followed by conventional therapy alone for additional 12 months</description>
    <arm_group_label>Sirolimus</arm_group_label>
    <other_name>Rapamune</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 - 65&#xD;
&#xD;
          -  Patients diagnosed as ADPKD based upon the unified criteria for ultrasonographic&#xD;
             diagnosis of ADPKD&#xD;
&#xD;
          -  Polycystic liver with total liver volume &gt; 2500 mL or symptomatic polycystic liver&#xD;
&#xD;
          -  Estimated glomerular filtration rate (IDMS-traceable MDRD equation) &gt;= 30&#xD;
             mL/min/1.73m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant systemic renal parenchymal or urinary tract disease (random urine&#xD;
             albumin-to-creatinine ratio &gt; 500 mg/g)&#xD;
&#xD;
          -  WBC &lt; 4,000/uL, platelet &lt; 100,000/uL, or hemoglobin &lt; 10.0 g/dL&#xD;
&#xD;
          -  Diabetes mellitus, cancer, or psychiatric disorder&#xD;
&#xD;
          -  Increased liver enzymes (2-fold above normal value)&#xD;
&#xD;
          -  Hypercholesterolemia (fasting cholesterol &gt; 200mg/dL) or hypertriglyceridemia (&gt;150&#xD;
             mg/dL) not controlled by lipid lowering therapy&#xD;
&#xD;
          -  Infection with hepatitis B, C, HIV&#xD;
&#xD;
          -  Any condition that could prevent full comprehension of the purpose and risks of the&#xD;
             study&#xD;
&#xD;
          -  Pregnant or lactating women or fertile women without effective contraception&#xD;
&#xD;
          -  History of intervention, such as cyst aspiration or embolization in past 1 year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Curie Ahn, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Curie Ahn, MD, PhD</last_name>
    <phone>82-2-2072-2222</phone>
    <email>curie@snu.ac.kr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>110-744</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Curie Ahn, MD, PhD</last_name>
      <phone>82-2-2072-2222</phone>
      <email>curie@snu.ac.kr</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 7, 2012</study_first_posted>
  <last_update_submitted>September 3, 2012</last_update_submitted>
  <last_update_submitted_qc>September 3, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 7, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Total liver volume</keyword>
  <keyword>Liver cyst</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Polycystic Kidney Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</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/NCT01680250
org study id: SILVER
nct id: NCT01680250
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to evaluate the effectiveness and safety of Sirolimus in
      reducing liver volume in autosomal dominant polycystic kidney disease.
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of end
      stage renal disease (ESRD), affecting an estimated 0.2% of population. Of ADPKD patients, 58%
      in 15-24 year, 85% in 25-34 year, and 94% in 35-46 year olds suffer from polycystic liver in
      addition to polycystic kidneys. Several anti-proliferative drugs have been used in clinical
      trials to stop cyst growth both in liver and kidneys. Among them, octreotide and sirolimus
      have been shown to be one of the most promising drugs to reduce cyst volume. Sirolimus
      already has been used as one of the most potential oral immunosuppressants. Moreover, the
      serum trough level is quite easy to measure. Sirolimus is the mTOR inhibitor that has been
      proven to be effective in reducing cyst growth both in animal models. However, its efficacy
      and safety is not well proven in previous studies. This is a open-label, prospective study to
      evaluate the effectiveness and safety of Sirolimus to reduce cyst growth in ADPKD patients
      with massive polycystic liver.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Total liver volume
time frame: 12 months
description: Change in total liver volume
measure: Total liver volume
time frame: 24 months
description: Change in total liver volume
measure: Total kidney volume
time frame: 12 month
description: Change in total kidney volume
measure: Estimated glomerular filtration rate
time frame: 12 month
description: Change in estimated glomerular filtration rate
measure: Urinary biomarker
time frame: 12 month
description: Urinary biomarker level
measure: Total kidney volume
time frame: 24 month
description: Change in total kidney volume
measure: Estimated glomerular filtration rate
time frame: 24 month
description: Change in estimated glomerular filtration rate
measure: Urinary biomarker
time frame: 24 month
description: Urinary biomarker level
measure: Abdominal pain
time frame: 12month
description: Abdominal pain quantified by Visual Analog Scale
measure: Abdominal pain
time frame: 24 month
description: Abdominal pain quantified by Visual Analog Scale
measure: Infection
time frame: 24 month
description: Incidence of infection event during study time
measure: Hospitalization
time frame: 24 month
description: Incidence of hospitalization due to adverse events during study time
measure: Drop out
time frame: 24 month
description: Incidence of discontinuation of study drug due to serious adverse events during study time
arm group label: Sirolimus
arm group type: Experimental
description: Sirolimus administration group starting dose: 2mg/day target trough level: 4-10 ng/dL
intervention type: Drug
intervention name: Sirolimus
description: Sirolimus administration for 12 months followed by conventional therapy alone for additional 12 months
arm group label: Sirolimus
other name: Rapamune
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Curie Ahn, MD, PhD
role: Principal Investigator
affiliation: Seoul National University Hospital
last name: Curie Ahn, MD, PhD
phone: 82-2-2072-2222
email: curie@snu.ac.kr
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Polycystic Kidney Diseases
mesh term: Sirolimus