<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/NCT03273413</url>
  </required_header>
  <id_info>
    <org_study_id>17-0678</org_study_id>
    <nct_id>NCT03273413</nct_id>
  </id_info>
  <brief_title>Statin Therapy in Patients With Early Stage ADPKD</brief_title>
  <official_title>Statin Therapy in Patients With Early Stage ADPKD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study plans to learn if pravastatin is helpful in slowing down the progression of kidney&#xD;
      disease in adults with autosomal dominant polycystic kidney disease (ADPKD). Pravastatin has&#xD;
      been approved by the Food and Drug Administration (FDA) for adults for treatment of&#xD;
      hyperlipidemia (high cholesterol levels). The investigators are using pravastatin in this&#xD;
      study as an investigational drug for treatment of ADPKD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, placebo-controlled trial designed to assess the efficacy&#xD;
      and benefits of pravastatin therapy in adults with ADPKD by evaluating 1) kidney volume as&#xD;
      measured by kidney magnetic resonance imaging (MRI); 2) renal blood flow as measured by&#xD;
      kidney magnetic resonance angiography (MRA); 3) kidney function as assessed by Glofil-125; 4)&#xD;
      plasma and urine protein markers that will allow a better understanding of how pravastatin&#xD;
      works in ADPKD; and 5) blood vessel stiffness as measured by carotid-femoral pulse wave&#xD;
      velocity. These parameters will be measured at baseline and after 2 years of pravastatin or&#xD;
      placebo treatment in 150 patients with ADPKD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 31, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2024</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Randomized, double-blind, placebo-controlled, parallel study design.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Total Kidney Volume</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Total kidney volume as assessed by renal MRI, at baseline and after 2 years of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Renal Blood Flow</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Renal blood flow, as assessed by renal MRA, at baseline and after 2 years of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Kidney Function</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Glomerular filtration rate (GFR), as assessed by Glofil-125, at baseline and after 2 years of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Circulating Inflammatory Markers</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Plasma levels of inflammatory cytokines and growth factors at baseline and after 2 years of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Circulating Markers of Oxidative Stress</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Plasma levels of oxidative stress markers at baseline and after 2 years of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Urinary Epithelial Cells</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Urinary epithelial cell protein expression, as assessed by immunofluorescence, at baseline and after 2 years of treatment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Blood Vessel Stiffness</measure>
    <time_frame>Baseline, 2 years</time_frame>
    <description>Blood vessel stiffness, as assessed by carotid-femoral pulse wave velocity, at baseline and after 2 years</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>ADPKD</condition>
  <condition>Autosomal Dominant Polycystic Kidney</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive inactive 40 mg tablets of placebo everyday for 6 weeks. If well tolerated, participants will continue taking inactive 40 mg dose of placebo everyday for 2 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pravastatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive 40 mg tablets of pravastatin everyday for 6 weeks. If well tolerated, participants will continue taking 40 mg dose of pravastatin everyday for 2 years.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pravastatin</intervention_name>
    <description>Anti-inflammatory, anti-oxidative stress, and anti-proliferative therapy</description>
    <arm_group_label>Pravastatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inactive tablet</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of ADPKD&#xD;
&#xD;
          -  Total kidney volume &gt;500 mL&#xD;
&#xD;
          -  Estimated glomerular filtration rate (GFR) ≥60 mL/min/1.73m^2&#xD;
&#xD;
          -  Controlled blood pressure &lt;140/80 mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Renal disease, renal cancer, single kidney, recent renal surgery, or acute kidney&#xD;
             injury&#xD;
&#xD;
          -  Unstable angina&#xD;
&#xD;
          -  Coronary artery disease&#xD;
&#xD;
          -  Prior ischemic stroke&#xD;
&#xD;
          -  Other clinical indication for a statin&#xD;
&#xD;
          -  History of hospitalizations within the last 3 months&#xD;
&#xD;
          -  Hepatic impairment or liver function abnormalities&#xD;
&#xD;
          -  Secondary hypercholesterolemia or hypocholesterolemia&#xD;
&#xD;
          -  Use of tolvaptan, gemfibrozil, other fibrates, niacin, clarithromycin, or cyclosporine&#xD;
&#xD;
          -  Hypersensitivity to statins&#xD;
&#xD;
          -  Immunosuppressive therapy within the last year&#xD;
&#xD;
          -  Clinical contraindication for an MRI (i.e. implants, pacemaker, claustrophobia)&#xD;
&#xD;
          -  Hypersensitivity to iodine&#xD;
&#xD;
          -  Pregnant or breast feeding&#xD;
&#xD;
          -  Current tobacco use&#xD;
&#xD;
          -  Alcohol abuse or dependence&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michel Chonchol, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Colorado Denver Anschutz Medical Campus</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Cadnapaphornchai MA, George DM, McFann K, Wang W, Gitomer B, Strain JD, Schrier RW. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2014 May;9(5):889-96. doi: 10.2215/CJN.08350813. Epub 2014 Apr 10.</citation>
    <PMID>24721893</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Pravastatin</keyword>
  <keyword>Statin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Kidney Diseases</mesh_term>
    <mesh_term>Polycystic Kidney, Autosomal Dominant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pravastatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03273413
org study id: 17-0678
nct id: NCT03273413
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study plans to learn if pravastatin is helpful in slowing down the progression of kidney
      disease in adults with autosomal dominant polycystic kidney disease (ADPKD). Pravastatin has
      been approved by the Food and Drug Administration (FDA) for adults for treatment of
      hyperlipidemia (high cholesterol levels). The investigators are using pravastatin in this
      study as an investigational drug for treatment of ADPKD.
This is a randomized, double-blind, placebo-controlled trial designed to assess the efficacy
      and benefits of pravastatin therapy in adults with ADPKD by evaluating 1) kidney volume as
      measured by kidney magnetic resonance imaging (MRI); 2) renal blood flow as measured by
      kidney magnetic resonance angiography (MRA); 3) kidney function as assessed by Glofil-125; 4)
      plasma and urine protein markers that will allow a better understanding of how pravastatin
      works in ADPKD; and 5) blood vessel stiffness as measured by carotid-femoral pulse wave
      velocity. These parameters will be measured at baseline and after 2 years of pravastatin or
      placebo treatment in 150 patients with ADPKD.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, double-blind, placebo-controlled, parallel study design.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Total Kidney Volume
time frame: Baseline, 2 years
description: Total kidney volume as assessed by renal MRI, at baseline and after 2 years of treatment
measure: Change in Renal Blood Flow
time frame: Baseline, 2 years
description: Renal blood flow, as assessed by renal MRA, at baseline and after 2 years of treatment
measure: Change in Kidney Function
time frame: Baseline, 2 years
description: Glomerular filtration rate (GFR), as assessed by Glofil-125, at baseline and after 2 years of treatment
measure: Change in Circulating Inflammatory Markers
time frame: Baseline, 2 years
description: Plasma levels of inflammatory cytokines and growth factors at baseline and after 2 years of treatment
measure: Change in Circulating Markers of Oxidative Stress
time frame: Baseline, 2 years
description: Plasma levels of oxidative stress markers at baseline and after 2 years of treatment
measure: Change in Urinary Epithelial Cells
time frame: Baseline, 2 years
description: Urinary epithelial cell protein expression, as assessed by immunofluorescence, at baseline and after 2 years of treatment
measure: Change in Blood Vessel Stiffness
time frame: Baseline, 2 years
description: Blood vessel stiffness, as assessed by carotid-femoral pulse wave velocity, at baseline and after 2 years
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive inactive 40 mg tablets of placebo everyday for 6 weeks. If well tolerated, participants will continue taking inactive 40 mg dose of placebo everyday for 2 years.
arm group label: Pravastatin
arm group type: Active Comparator
description: Participants will receive 40 mg tablets of pravastatin everyday for 6 weeks. If well tolerated, participants will continue taking 40 mg dose of pravastatin everyday for 2 years.
intervention type: Drug
intervention name: Pravastatin
description: Anti-inflammatory, anti-oxidative stress, and anti-proliferative therapy
arm group label: Pravastatin
intervention type: Drug
intervention name: Placebo
description: Inactive tablet
arm group label: Placebo
criteria: 
gender: All
minimum age: 25 Years
maximum age: 60 Years
healthy volunteers: No
last name: Michel Chonchol, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
facility: 
country: United States
citation: Cadnapaphornchai MA, George DM, McFann K, Wang W, Gitomer B, Strain JD, Schrier RW. Effect of pravastatin on total kidney volume, left ventricular mass index, and microalbuminuria in pediatric autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2014 May;9(5):889-96. doi: 10.2215/CJN.08350813. Epub 2014 Apr 10.
PMID: 24721893
responsible party type: Sponsor
mesh term: Polycystic Kidney Diseases
mesh term: Polycystic Kidney, Autosomal Dominant
mesh term: Pravastatin
sharing ipd: No