<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/NCT03254563</url>
  </required_header>
  <id_info>
    <org_study_id>17-1160</org_study_id>
    <nct_id>NCT03254563</nct_id>
  </id_info>
  <brief_title>Copeptin and Nonalcoholic Fatty Liver Disease</brief_title>
  <official_title>Copeptin and Nonalcoholic Fatty Liver Disease</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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Copeptin, a surrogate marker for vasopressin, has been found to be elevated in metabolic&#xD;
      disorders including obesity and diabetes, which are disorders both associated with&#xD;
      nonalcoholic fatty liver disease (NAFLD), and therefore suggest a potential role for&#xD;
      vasopressin in the pathogenesis of NAFLD. The investigators intend to investigate if there is&#xD;
      an association of vasopressin with the presence and severity of NAFLD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants: As a pilot study, the investigators will recruit 30 obese adults with NAFLD&#xD;
      based upon ultrasound echogenicity within 6 months of enrollment, and 30 obese adults without&#xD;
      NAFLD based upon ultrasound (US) echogenicity for comparison.&#xD;
&#xD;
      Screening Visit/Study Visit: Patients in the investigator's Obesity clinic will be approached&#xD;
      about the study and consented if interested at the screening. Participants will have a chart&#xD;
      review for their history and physical Exam and medication review for inclusion and exclusion&#xD;
      criteria. Qualified participants will be invited for a screening visit to be scheduled in&#xD;
      conjunction with the labs and procedures performed as Standard of Care (SOC) in the obesity&#xD;
      clinic. At the screening visit, following consent, participants will have vitals (blood&#xD;
      pressure, Body Mass Index (BMI), waist circumference) and a physical examination performed.&#xD;
      Participants' Standard of Care (SOC) labs including fasting lipid panel, HbA1c (unless done&#xD;
      within last 3 months), comprehensive metabolic panel, titers for hepatitis b and c, and&#xD;
      complete blood count will be drawn, along with the following research labs: insulin,&#xD;
      glucagon, free fatty acids, adiponectin and a 24-hour urine cortisol collection. Those who&#xD;
      have not had an abdominal US will have a SOC US performed to delineate non-NAFLD or NAFLD&#xD;
      status. US will not be performed if already done within 6 months of enrollment. All&#xD;
      ultrasound studies will be interpreted by one University of Colorado Denver radiologist to&#xD;
      categorize the patient as NAFLD or non-NAFLD to limit inter-reader variability. Those with&#xD;
      NAFLD present on US will also have a SOC Fibroscan done to assess severity of steatosis&#xD;
      (based upon Controlled Attenuation Parameter or CAP Score) and fibrosis (based upon&#xD;
      elastography). Given limitations of ultrasound to accurately detect significant steatosis&#xD;
      unless &gt;30%, the investigators will in addition perform Fibroscan (all particpants regardless&#xD;
      of US) to assess steatosis, so as to confirm if significant steatosis and compare copeptin&#xD;
      levels on a continuum of level of steatosis as part of research procedure. Fibroscan can&#xD;
      detect steatosis (based upon Controlled Attenuation Parameter or CAP Score) and fibrosis&#xD;
      (based upon elastography). FIbroscan with M probe has been found to have AUROC 0.823 for a&#xD;
      cutoff of value of 248 dB/m for no steatosis vs steatosis (with other cutoffs at 268 dB/m&#xD;
      between S1 and S2-S3 and 280 dB/m between S1-S2 and S3 disease).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 19, 2018</start_date>
  <completion_date type="Anticipated">June 2021</completion_date>
  <primary_completion_date type="Anticipated">June 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Comparision of Copeptin with and without NAFLD</measure>
    <time_frame>Within 6 months of documented NAFLD or non-NAFLD and within 1 week of fibroscan</time_frame>
    <description>The investigators will compare level of copeptin with the measurement of NAFLD based upon ultrasound and fibroscan.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Copeptin and level of steatosis</measure>
    <time_frame>Within one week of fibroscan being perfomed</time_frame>
    <description>Comparison of CAP score of fibroscan to copeptin levels</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Copeptin and Liver Elastography</measure>
    <time_frame>Within one week of fibroscan being perfomed</time_frame>
    <description>Compare Copeptin to liver elastography (kPa)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin Resistance and copeptin</measure>
    <time_frame>Same day as these labs after 8 hour fast from food and water.</time_frame>
    <description>Changes in insulin, fasting glucose, HOMA-IR, HOMA-B, adiponectin estimated Insulin Compared to copeptin level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Copeptin and Lipids</measure>
    <time_frame>Same day as these labs after 8 hour fast from food and water.</time_frame>
    <description>Compare copeptin level to cholesterol and free fatty acids</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Copeptin and Liver enzymes</measure>
    <time_frame>Same day as these labs after 8 hour fast from food and water.</time_frame>
    <description>Compare copeptin and liver enzymes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Copeptin and Weight</measure>
    <time_frame>Within 1 month of screening visit</time_frame>
    <description>Compare Copeptin with BMI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Copeptin and Waist Circumference</measure>
    <time_frame>Within 1 month of screening visit</time_frame>
    <description>Compare copeptin with weight circumference</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Copeptin and Blood pressure</measure>
    <time_frame>Within 1 month of screening visit</time_frame>
    <description>Compare copetin with measurements of blood pressure</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">60</enrollment>
  <condition>NAFLD</condition>
  <arm_group>
    <arm_group_label>Obese with NAFLD</arm_group_label>
    <description>Patients who have NAFLD based upon ultrasound</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Obese without NAFLD</arm_group_label>
    <description>Patients who do not have NAFLD based upon ultrasound</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum and urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        1. Obese adults (BMI 30-40 kg/m2) age 30-75 years with NAFLD based upon ultrasound&#xD;
             echogenicity within 6 months of enrollment&#xD;
&#xD;
          2. Obese adults (BMI 30-40 kg/m2) age 30-75 years without NAFLD based upon ultrasound&#xD;
             echogenicity within 6 months of enrollment&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients age 30-75&#xD;
&#xD;
          2. BMI 30-40&#xD;
&#xD;
          3. Presence of fatty liver on ultrasound&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diabetes mellitus (determined by prior HbA1c, fasting glucose, and/or random glucose&#xD;
             in the last three months according to ADA criteria),&#xD;
&#xD;
          2. Medication known to affect insulin sensitivity e.g. metformin, thiazolidinediones,&#xD;
             systemic steroids, atypical antipsychotics),&#xD;
&#xD;
          3. Fibrates,&#xD;
&#xD;
          4. eGFR &lt;45 ml/min/1.73m2 by MDRD equation(11),&#xD;
&#xD;
          5. Pregnancy,&#xD;
&#xD;
          6. Breast feeding,&#xD;
&#xD;
          7. Sodium &lt;135 mEq/L,&#xD;
&#xD;
          8. Diabetes insipidus,&#xD;
&#xD;
          9. Liver disease other than NAFLD (including obstructive liver disease),&#xD;
&#xD;
         10. ALT or AST&gt;60 IU/L,&#xD;
&#xD;
         11. Hepatic steatosis on ultrasound for the non-NAFLD group,&#xD;
&#xD;
         12. Congestive heart failure,&#xD;
&#xD;
         13. Patients who consume &gt;20g of ETOH a day,&#xD;
&#xD;
         14. Patients found to have Cushing's disease based upon 24 hour urine results (Urine Free&#xD;
             cortisol &gt;2x upper limit of normal).&#xD;
&#xD;
         15. Patient's with pacemakers&#xD;
&#xD;
         16. Off of Coenzyme Q for 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Jensen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Thomas Jensen, MD</last_name>
    <phone>7208482650</phone>
    <email>thomas.jensen@ucdenver.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kristen Nadeau, MD</last_name>
    <phone>(720) 777-6128</phone>
    <email>Kristen.Nadeau@childrenscolorado.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Jensen, MD</last_name>
      <phone>720-848-2650</phone>
    </contact>
    <contact_backup>
      <last_name>Kristen Nadeau, MD</last_name>
      <phone>720-777-2855</phone>
      <email>Kristen.Nadeau@childrenscolorado.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>August 16, 2017</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>February 9, 2021</last_update_submitted>
  <last_update_submitted_qc>February 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2021</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>Liver Diseases</mesh_term>
    <mesh_term>Fatty Liver</mesh_term>
    <mesh_term>Non-alcoholic Fatty Liver Disease</mesh_term>
  </condition_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/NCT03254563
org study id: 17-1160
nct id: NCT03254563
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Copeptin, a surrogate marker for vasopressin, has been found to be elevated in metabolic
      disorders including obesity and diabetes, which are disorders both associated with
      nonalcoholic fatty liver disease (NAFLD), and therefore suggest a potential role for
      vasopressin in the pathogenesis of NAFLD. The investigators intend to investigate if there is
      an association of vasopressin with the presence and severity of NAFLD.
Participants: As a pilot study, the investigators will recruit 30 obese adults with NAFLD
      based upon ultrasound echogenicity within 6 months of enrollment, and 30 obese adults without
      NAFLD based upon ultrasound (US) echogenicity for comparison.

      Screening Visit/Study Visit: Patients in the investigator's Obesity clinic will be approached
      about the study and consented if interested at the screening. Participants will have a chart
      review for their history and physical Exam and medication review for inclusion and exclusion
      criteria. Qualified participants will be invited for a screening visit to be scheduled in
      conjunction with the labs and procedures performed as Standard of Care (SOC) in the obesity
      clinic. At the screening visit, following consent, participants will have vitals (blood
      pressure, Body Mass Index (BMI), waist circumference) and a physical examination performed.
      Participants' Standard of Care (SOC) labs including fasting lipid panel, HbA1c (unless done
      within last 3 months), comprehensive metabolic panel, titers for hepatitis b and c, and
      complete blood count will be drawn, along with the following research labs: insulin,
      glucagon, free fatty acids, adiponectin and a 24-hour urine cortisol collection. Those who
      have not had an abdominal US will have a SOC US performed to delineate non-NAFLD or NAFLD
      status. US will not be performed if already done within 6 months of enrollment. All
      ultrasound studies will be interpreted by one University of Colorado Denver radiologist to
      categorize the patient as NAFLD or non-NAFLD to limit inter-reader variability. Those with
      NAFLD present on US will also have a SOC Fibroscan done to assess severity of steatosis
      (based upon Controlled Attenuation Parameter or CAP Score) and fibrosis (based upon
      elastography). Given limitations of ultrasound to accurately detect significant steatosis
      unless >30%, the investigators will in addition perform Fibroscan (all particpants regardless
      of US) to assess steatosis, so as to confirm if significant steatosis and compare copeptin
      levels on a continuum of level of steatosis as part of research procedure. Fibroscan can
      detect steatosis (based upon Controlled Attenuation Parameter or CAP Score) and fibrosis
      (based upon elastography). FIbroscan with M probe has been found to have AUROC 0.823 for a
      cutoff of value of 248 dB/m for no steatosis vs steatosis (with other cutoffs at 268 dB/m
      between S1 and S2-S3 and 280 dB/m between S1-S2 and S3 disease).
observational model: Other
time perspective: Cross-Sectional
measure: Comparision of Copeptin with and without NAFLD
time frame: Within 6 months of documented NAFLD or non-NAFLD and within 1 week of fibroscan
description: The investigators will compare level of copeptin with the measurement of NAFLD based upon ultrasound and fibroscan.
measure: Copeptin and level of steatosis
time frame: Within one week of fibroscan being perfomed
description: Comparison of CAP score of fibroscan to copeptin levels
measure: Copeptin and Liver Elastography
time frame: Within one week of fibroscan being perfomed
description: Compare Copeptin to liver elastography (kPa)
measure: Insulin Resistance and copeptin
time frame: Same day as these labs after 8 hour fast from food and water.
description: Changes in insulin, fasting glucose, HOMA-IR, HOMA-B, adiponectin estimated Insulin Compared to copeptin level
measure: Copeptin and Lipids
time frame: Same day as these labs after 8 hour fast from food and water.
description: Compare copeptin level to cholesterol and free fatty acids
measure: Copeptin and Liver enzymes
time frame: Same day as these labs after 8 hour fast from food and water.
description: Compare copeptin and liver enzymes
measure: Copeptin and Weight
time frame: Within 1 month of screening visit
description: Compare Copeptin with BMI
measure: Copeptin and Waist Circumference
time frame: Within 1 month of screening visit
description: Compare copeptin with weight circumference
measure: Copeptin and Blood pressure
time frame: Within 1 month of screening visit
description: Compare copetin with measurements of blood pressure
arm group label: Obese with NAFLD
description: Patients who have NAFLD based upon ultrasound
arm group label: Obese without NAFLD
description: Patients who do not have NAFLD based upon ultrasound
Serum and urine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: Thomas Jensen, MD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Thomas Jensen, MD
phone: 7208482650
email: thomas.jensen@ucdenver.edu
last name: Kristen Nadeau, MD
phone: (720) 777-6128
email: Kristen.Nadeau@childrenscolorado.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
mesh term: Fatty Liver
mesh term: Non-alcoholic Fatty Liver Disease
sharing ipd: No