<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/NCT04407481</url>
  </required_header>
  <id_info>
    <org_study_id>20-0277</org_study_id>
    <nct_id>NCT04407481</nct_id>
  </id_info>
  <brief_title>PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN)</brief_title>
  <acronym>PENGUIN</acronym>
  <official_title>PENGUIN: PErfusioN, OxyGen ConsUmptIon and ENergetics in 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>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of&#xD;
      end-stage kidney disease (ESKD). The disorder is characterized by development and continued&#xD;
      growth of multiple cysts requiring renal replacement therapy in 50% of patients by age 60&#xD;
      years. However, ADPKD is also a complex metabolic disorder defined by insulin resistance (IR)&#xD;
      and mitochondrial dysfunction which may be causally related to cyst expansion, kidney&#xD;
      function decline and contribute to reduced life expectancy. Renal hypoxia, stemming from a&#xD;
      potential metabolic mismatch between increased renal energy expenditure and impaired&#xD;
      substrate utilization, is proposed as a novel unifying early pathway in the development and&#xD;
      expansion of renal cysts in ADPKD. By examining the interplay between renal O2 consumption&#xD;
      and energy utilization in young adults with and without ADPKD, the investigators hope to&#xD;
      identify novel therapeutic targets to impede development of cyst expansion in future trials.&#xD;
&#xD;
      The investigators propose to address the specific aims in a cross-sectional study with 20&#xD;
      adults with ADPKD (50% female, ages 18-40 years). Comparative data will be provided from&#xD;
      healthy adults from an ongoing study with similar study design and methods (CROCODILE Study:&#xD;
      Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance). For&#xD;
      this protocol, participants will complete a one day study visit at Children's Hospital&#xD;
      Colorado. Patients will undergo a dual energy x-ray absorptiometry (DXA) to assess body&#xD;
      composition, and a 11C-acetate positron emission tomography (PET/CT) scan to quantify renal&#xD;
      O2 consumption. After the PET/CT, participants will undergo a hyperinsulinemic-euglycemic&#xD;
      clamp while fasting to quantify insulin sensitivity. Glomerular Filtration Rate (GFR) and&#xD;
      Effective Renal Plasma Flow (ERPF) will be measured by iohexol and PAH clearances during the&#xD;
      hyperinsulinemic-euglycemic clamp.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 1, 2020</start_date>
  <completion_date type="Actual">October 13, 2022</completion_date>
  <primary_completion_date type="Actual">October 13, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Renal oxygen consumption</measure>
    <time_frame>30 minutes</time_frame>
    <description>11-C Acetate PET/CT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Insulin Sensitivity</measure>
    <time_frame>4.5 hours</time_frame>
    <description>Hyperinsulinemic-Euglycemic Clamp</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mitochondrial Function</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for mitochondrial DNA copy number</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mitochondrial Function</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for untargeted metabolite assessment of the tricyclic acid (TCA) cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mitochondrial Function</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for targeted assessment and quantification of glucose oxidation using an established metabolite panel</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mitochondrial Function</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glomerular Filtration Rate (GFR)</measure>
    <time_frame>3 hours</time_frame>
    <description>Iohexol Clearance Study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effective Renal Plasma Flow (ERPF)</measure>
    <time_frame>2.5 hours</time_frame>
    <description>PAH Clearance Study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renin-Angiotensin-Aldosterone-System Activity</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Plasma Renin levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renin-Angiotensin-Aldosterone-System Activity</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Angiotensin II levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renin-Angiotensin-Aldosterone-System Activity</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Copeptin levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Injury Biomarkers</measure>
    <time_frame>5 minutes</time_frame>
    <description>Chitinase-3-like protein 1 (YKL-40) levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Injury Biomarkers</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Neutrophil gelatinase-associated lipocalin (NGAL) levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Injury Biomarkers</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Kidney Injury Molecule 1 (KIM-1) levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Injury Biomarkers</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Interleukin-18 (IL-18) levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Injury Biomarkers</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for Tumor Necrosis Factor Receptor 1/2 (TNF-R 1/2) levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Injury Biomarkers</measure>
    <time_frame>5 minutes</time_frame>
    <description>Blood draw for monocyte chemoattractant protein-1 (MCP-1) levels</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">22</enrollment>
  <condition>Polycystic Kidney Disease, Adult</condition>
  <condition>Polycystic Kidney, Autosomal Dominant</condition>
  <arm_group>
    <arm_group_label>Adults with autosomal dominant polycystic kidney disease</arm_group_label>
    <description>All participants will undergo DXA scan, PET/CT using 11-C acetate to measure renal oxygen consumption, hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity, and renal clearance testing using iohexol and para-aminohippurate (PAH) to quantify glomerular filtration rate (GFR) and effective renal plasma flow (ERPF).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Comparative data will be provided from healthy adults from an ongoing study with similar study design and methods (CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aminohippurate Sodium Inj 20%</intervention_name>
    <description>Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)</description>
    <arm_group_label>Adults with autosomal dominant polycystic kidney disease</arm_group_label>
    <other_name>•- Sodium 4-amino hippurate (PAH) inj 20% 2g/10 milliliter (mL) • Para-aminohippurate • Aminohippuric acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Iohexol Inj 300 milligrams per milliliter (MG/ML)</intervention_name>
    <description>Diagnostic aid/agent used to measure glomerular filtration rate (GFR)</description>
    <arm_group_label>Adults with autosomal dominant polycystic kidney disease</arm_group_label>
    <other_name>omnipaque 300</other_name>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>PET/CT Scan</intervention_name>
    <description>Imaging used to visualize the kidneys and quantify renal metabolic activity</description>
    <arm_group_label>Adults with autosomal dominant polycystic kidney disease</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      During the study, we will collect blood and urine samples for assessment of kidney function&#xD;
      and kidney injury markers.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The investigators propose to address the specific aims in a cross-sectional study with 20&#xD;
        adults with ADPKD (50% female, ages 18-40 years). Comparative data will be provided from&#xD;
        healthy adults from an ongoing study with similar study design and methods.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with Autosomal dominant polycystic kidney disease&#xD;
&#xD;
          -  Age 18-40 years&#xD;
&#xD;
          -  BMI &gt;= 18.5 and &lt;30 kg/m2&#xD;
&#xD;
          -  Weight &lt;350 lbs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diabetes mellitus, based on previous diagnosis&#xD;
&#xD;
          -  Albuminuria (≥30mg/g) or estimated glomerular filtration rate (eGFR) &lt;75ml/min/1.73m2&#xD;
&#xD;
          -  Pregnancy or nursing&#xD;
&#xD;
          -  Anemia&#xD;
&#xD;
          -  Allergy to shellfish or iodine&#xD;
&#xD;
          -  Vaptan therapy (e.g. tolvaptan)&#xD;
&#xD;
          -  Uncontrolled hypertension (average ≥140/90 mmHg)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Children's Hospital Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2023</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>Kidney Diseases</mesh_term>
    <mesh_term>Polycystic Kidney Diseases</mesh_term>
    <mesh_term>Polycystic Kidney, Autosomal Dominant</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04407481
org study id: 20-0277
nct id: NCT04407481
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of
      end-stage kidney disease (ESKD). The disorder is characterized by development and continued
      growth of multiple cysts requiring renal replacement therapy in 50% of patients by age 60
      years. However, ADPKD is also a complex metabolic disorder defined by insulin resistance (IR)
      and mitochondrial dysfunction which may be causally related to cyst expansion, kidney
      function decline and contribute to reduced life expectancy. Renal hypoxia, stemming from a
      potential metabolic mismatch between increased renal energy expenditure and impaired
      substrate utilization, is proposed as a novel unifying early pathway in the development and
      expansion of renal cysts in ADPKD. By examining the interplay between renal O2 consumption
      and energy utilization in young adults with and without ADPKD, the investigators hope to
      identify novel therapeutic targets to impede development of cyst expansion in future trials.

      The investigators propose to address the specific aims in a cross-sectional study with 20
      adults with ADPKD (50% female, ages 18-40 years). Comparative data will be provided from
      healthy adults from an ongoing study with similar study design and methods (CROCODILE Study:
      Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance). For
      this protocol, participants will complete a one day study visit at Children's Hospital
      Colorado. Patients will undergo a dual energy x-ray absorptiometry (DXA) to assess body
      composition, and a 11C-acetate positron emission tomography (PET/CT) scan to quantify renal
      O2 consumption. After the PET/CT, participants will undergo a hyperinsulinemic-euglycemic
      clamp while fasting to quantify insulin sensitivity. Glomerular Filtration Rate (GFR) and
      Effective Renal Plasma Flow (ERPF) will be measured by iohexol and PAH clearances during the
      hyperinsulinemic-euglycemic clamp.
observational model: Cohort
time perspective: Cross-Sectional
measure: Renal oxygen consumption
time frame: 30 minutes
description: 11-C Acetate PET/CT
measure: Insulin Sensitivity
time frame: 4.5 hours
description: Hyperinsulinemic-Euglycemic Clamp
measure: Mitochondrial Function
time frame: 5 minutes
description: Blood draw for mitochondrial DNA copy number
measure: Mitochondrial Function
time frame: 5 minutes
description: Blood draw for untargeted metabolite assessment of the tricyclic acid (TCA) cycle
measure: Mitochondrial Function
time frame: 5 minutes
description: Blood draw for targeted assessment and quantification of glucose oxidation using an established metabolite panel
measure: Mitochondrial Function
time frame: 5 minutes
description: Blood draw for untargeted metabolite assessment of Free Fatty Acid (FFA) oxidation
measure: Glomerular Filtration Rate (GFR)
time frame: 3 hours
description: Iohexol Clearance Study
measure: Effective Renal Plasma Flow (ERPF)
time frame: 2.5 hours
description: PAH Clearance Study
measure: Renin-Angiotensin-Aldosterone-System Activity
time frame: 5 minutes
description: Blood draw for Plasma Renin levels
measure: Renin-Angiotensin-Aldosterone-System Activity
time frame: 5 minutes
description: Blood draw for Angiotensin II levels
measure: Renin-Angiotensin-Aldosterone-System Activity
time frame: 5 minutes
description: Blood draw for Copeptin levels
measure: Kidney Injury Biomarkers
time frame: 5 minutes
description: Chitinase-3-like protein 1 (YKL-40) levels
measure: Kidney Injury Biomarkers
time frame: 5 minutes
description: Blood draw for Neutrophil gelatinase-associated lipocalin (NGAL) levels
measure: Kidney Injury Biomarkers
time frame: 5 minutes
description: Blood draw for Kidney Injury Molecule 1 (KIM-1) levels
measure: Kidney Injury Biomarkers
time frame: 5 minutes
description: Blood draw for Interleukin-18 (IL-18) levels
measure: Kidney Injury Biomarkers
time frame: 5 minutes
description: Blood draw for Tumor Necrosis Factor Receptor 1/2 (TNF-R 1/2) levels
measure: Kidney Injury Biomarkers
time frame: 5 minutes
description: Blood draw for monocyte chemoattractant protein-1 (MCP-1) levels
arm group label: Adults with autosomal dominant polycystic kidney disease
description: All participants will undergo DXA scan, PET/CT using 11-C acetate to measure renal oxygen consumption, hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity, and renal clearance testing using iohexol and para-aminohippurate (PAH) to quantify glomerular filtration rate (GFR) and effective renal plasma flow (ERPF).
arm group label: Healthy Controls
description: Comparative data will be provided from healthy adults from an ongoing study with similar study design and methods (CROCODILE Study: Control of Renal Oxygen Consumption, Mitochondrial Dysfunction, and Insulin Resistance).
intervention type: Drug
intervention name: Aminohippurate Sodium Inj 20%
description: Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)
arm group label: Adults with autosomal dominant polycystic kidney disease
other name: •- Sodium 4-amino hippurate (PAH) inj 20% 2g/10 milliliter (mL) • Para-aminohippurate • Aminohippuric acid
intervention type: Drug
intervention name: Iohexol Inj 300 milligrams per milliliter (MG/ML)
description: Diagnostic aid/agent used to measure glomerular filtration rate (GFR)
arm group label: Adults with autosomal dominant polycystic kidney disease
other name: omnipaque 300
intervention type: Radiation
intervention name: PET/CT Scan
description: Imaging used to visualize the kidneys and quantify renal metabolic activity
arm group label: Adults with autosomal dominant polycystic kidney disease
During the study, we will collect blood and urine samples for assessment of kidney function
      and kidney injury markers.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Polycystic Kidney Diseases
mesh term: Polycystic Kidney, Autosomal Dominant
sharing ipd: Undecided