<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/NCT03803124</url>
  </required_header>
  <id_info>
    <org_study_id>FHM-1-2015</org_study_id>
    <nct_id>NCT03803124</nct_id>
  </id_info>
  <brief_title>Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD</brief_title>
  <acronym>POLY</acronym>
  <official_title>Effect of Tolvaptan on Renal Plasma Flow (RPF) and Glomerular Filtration Rate (GFR) in ADPKD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regional Hospital Holstebro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Regional Hospital Holstebro</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Polycystic kidney disease (ADPKD) is a common genetic disorder, characterized by the&#xD;
      formation of cysts in the kidneys, causing gradual renal function-loss. Previous studies have&#xD;
      shown that, reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) play a role&#xD;
      in the progression of renal disease in ADPKD. Tolvaptan is a vasopressin 2 antagonist, which&#xD;
      seems to reduce the growth of total kidney volume (TKV) and the decline in e-GFR in ADPKD.&#xD;
      The mechanism is not fully understood and could, at least partly, be caused by stimulation of&#xD;
      the renal blood flow. The purpose of this trial is to investigate if tolvaptan´s improve&#xD;
      renal blood flow and glomerular filtration in ADPKD, in a randomized, cross-over,&#xD;
      double-blind, placebo-controlled study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The aim is to measure the acute effects of tolvaptan on:&#xD;
&#xD;
        1. Renal hemodynamics (RPF, GFR, filtration fraction ((FF)) and renovascular resistance&#xD;
           ((RVR))&#xD;
&#xD;
        2. Blood pressure (central blood pressure ((cBP)) and brachial blood pressure bBP)&#xD;
&#xD;
        3. Several vasoactive hormones (plasma renin ((PRC)), plasma angiotensin II ((p-Ang-II)),&#xD;
           plasma aldosterone ((p-Aldo)), plasma vasopressin ((p-AVP))&#xD;
&#xD;
      in patients with ADPKD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2015</start_date>
  <completion_date type="Actual">December 15, 2017</completion_date>
  <primary_completion_date type="Actual">December 15, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal plasma flow (RPF)</measure>
    <time_frame>Two hours after trial medicine intake</time_frame>
    <description>Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Central and brachial blood pressures (BP)</measure>
    <time_frame>Measured every 15 minutes during the examination day</time_frame>
    <description>Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glomerular filtration rate (GFR)</measure>
    <time_frame>Two hours after trial medicine intake</time_frame>
    <description>Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Filtration fraction (FF)</measure>
    <time_frame>Two hours after trial medicine intake</time_frame>
    <description>Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= %)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of vasopressin (p-AVP)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Blood samples (unit of measurement= pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of aldosterone (p-Aldo)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Blood samples (unit of measurement= pmol/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of angiotensin II (p-AngII)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Blood samples (unit of measurement= pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration of renin (PRC)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Blood samples (unit of measurement= pg/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine excretion of aquaporin 2 (u-AQP2)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Urine sample (unit of measurement= ng/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine output (OU)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Urine sample (unit of measurement= ml/min)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine osmolality (U-osm)</measure>
    <time_frame>measured before and 3 hours after trial medicine intake</time_frame>
    <description>Urine sample (unit of measurement= mosmol/kg)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fractional excretion of sodium (FENa)</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Blood and urine sample (unit of measurement= %)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Albumin excretion rate</measure>
    <time_frame>Measured before and 3 hours after trial medicine intake</time_frame>
    <description>Blood and urine sample (unit of measurement= mg/min)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Polycystic Kidney, Autosomal Dominant</condition>
  <arm_group>
    <arm_group_label>Tolvaptan</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Tolvaptan&#xD;
1 tablet before renography</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo&#xD;
1 tablet before renography</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolvaptan</intervention_name>
    <description>1 tablet before renography</description>
    <arm_group_label>Tolvaptan</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>1 tablet before renography</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Diagnosis with ADPKD&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
          -  Contraception for fertile women&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Renal transplantation&#xD;
&#xD;
          -  Operation in the kidney&#xD;
&#xD;
          -  Diabetes mellitus&#xD;
&#xD;
          -  Neoplastic conditions&#xD;
&#xD;
          -  Pregnancy, nursing&#xD;
&#xD;
          -  Unwillingness to participate&#xD;
&#xD;
          -  eGFR &gt; 30&#xD;
&#xD;
          -  Intolerance towards tolvaptan&#xD;
&#xD;
          -  Alcohol or medical abuse,&#xD;
&#xD;
          -  BP &gt;&gt;170/110 blood pressure despite regulation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Frank Mose, MD, Ph D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Departments of medical research and medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Departments of medical research and medicine</name>
      <address>
        <city>Holstebro</city>
        <zip>7500</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>January 10, 2019</last_update_submitted>
  <last_update_submitted_qc>January 10, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Regional Hospital Holstebro</investigator_affiliation>
    <investigator_full_name>Erling Bjerregaard Pedersen</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>CYSTS, KIDNEYS</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>Tolvaptan</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/NCT03803124
org study id: FHM-1-2015
nct id: NCT03803124
lead sponsor: 
has dmc: Yes
Polycystic kidney disease (ADPKD) is a common genetic disorder, characterized by the
      formation of cysts in the kidneys, causing gradual renal function-loss. Previous studies have
      shown that, reduced glomerular filtration rate (GFR) and renal plasma flow (RPF) play a role
      in the progression of renal disease in ADPKD. Tolvaptan is a vasopressin 2 antagonist, which
      seems to reduce the growth of total kidney volume (TKV) and the decline in e-GFR in ADPKD.
      The mechanism is not fully understood and could, at least partly, be caused by stimulation of
      the renal blood flow. The purpose of this trial is to investigate if tolvaptan´s improve
      renal blood flow and glomerular filtration in ADPKD, in a randomized, cross-over,
      double-blind, placebo-controlled study.
The aim is to measure the acute effects of tolvaptan on:

        1. Renal hemodynamics (RPF, GFR, filtration fraction ((FF)) and renovascular resistance
           ((RVR))

        2. Blood pressure (central blood pressure ((cBP)) and brachial blood pressure bBP)

        3. Several vasoactive hormones (plasma renin ((PRC)), plasma angiotensin II ((p-Ang-II)),
           plasma aldosterone ((p-Aldo)), plasma vasopressin ((p-AVP))

      in patients with ADPKD.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Triple (Participant, Care Provider, Investigator)
measure: Renal plasma flow (RPF)
time frame: Two hours after trial medicine intake
description: Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)
measure: Central and brachial blood pressures (BP)
time frame: Measured every 15 minutes during the examination day
description: Measured using Mobil-O-Graph® PWA (unit of measurement= mmHg)
measure: Glomerular filtration rate (GFR)
time frame: Two hours after trial medicine intake
description: Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= ml/min)
measure: Filtration fraction (FF)
time frame: Two hours after trial medicine intake
description: Estimated by posterior Technetium-99m diethylenetriamine penta-acetic acid (99-mTc-DTPA) renography 2 hours after trial medicine intake. (unit of measurement= %)
measure: Plasma concentration of vasopressin (p-AVP)
time frame: Measured before and 3 hours after trial medicine intake
description: Blood samples (unit of measurement= pg/ml)
measure: Plasma concentration of aldosterone (p-Aldo)
time frame: Measured before and 3 hours after trial medicine intake
description: Blood samples (unit of measurement= pmol/ml)
measure: Plasma concentration of angiotensin II (p-AngII)
time frame: Measured before and 3 hours after trial medicine intake
description: Blood samples (unit of measurement= pg/ml)
measure: Plasma concentration of renin (PRC)
time frame: Measured before and 3 hours after trial medicine intake
description: Blood samples (unit of measurement= pg/ml)
measure: Urine excretion of aquaporin 2 (u-AQP2)
time frame: Measured before and 3 hours after trial medicine intake
description: Urine sample (unit of measurement= ng/ml)
measure: Urine output (OU)
time frame: Measured before and 3 hours after trial medicine intake
description: Urine sample (unit of measurement= ml/min)
measure: Urine osmolality (U-osm)
time frame: measured before and 3 hours after trial medicine intake
description: Urine sample (unit of measurement= mosmol/kg)
measure: Fractional excretion of sodium (FENa)
time frame: Measured before and 3 hours after trial medicine intake
description: Blood and urine sample (unit of measurement= %)
measure: Albumin excretion rate
time frame: Measured before and 3 hours after trial medicine intake
description: Blood and urine sample (unit of measurement= mg/min)
arm group label: Tolvaptan
arm group type: Active Comparator
description: Drug: Tolvaptan
1 tablet before renography
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
1 tablet before renography
intervention type: Drug
intervention name: Tolvaptan
description: 1 tablet before renography
arm group label: Tolvaptan
intervention type: Drug
intervention name: Placebo
description: 1 tablet before renography
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Frank Mose, MD, Ph D
role: Principal Investigator
affiliation: Departments of medical research and medicine
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Regional Hospital Holstebro
investigator full name: Erling Bjerregaard Pedersen
investigator title: Professor
mesh term: Polycystic Kidney Diseases
mesh term: Polycystic Kidney, Autosomal Dominant
mesh term: Tolvaptan