<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/NCT02237521</url>
  </required_header>
  <id_info>
    <org_study_id>H-2-2014-021</org_study_id>
    <nct_id>NCT02237521</nct_id>
  </id_info>
  <brief_title>The Effect of the Incretin Hormones on the Endocrine Pancreatic Function During Hyperglycemia in End-stage Renal Disease</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bo Feldt-Rasmussen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with end-stage renal disease (ESRD) have a high prevalence of impaired glucose&#xD;
      metabolism. The pathophysiological cause is uncertain, but disturbances in the secretion,&#xD;
      elimination and effect of glucagon, insulin and the two incretin hormones glucagon-like&#xD;
      peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), probably play&#xD;
      important roles. Our research group has previously found that dialysis patients without type&#xD;
      2 diabetes mellitus (T2DM) have a reduced incretin effect and an inability to suppress&#xD;
      glucagon after a meal - two early pathophysiological characteristics of patients with T2DM&#xD;
      and normal kidney function.&#xD;
&#xD;
      The aim of the project is to provide a detailed description of the mechanisms underlying the&#xD;
      (patho)physiological effects of the incretin hormones in patients with ESRD. We plan to&#xD;
      investigate the above mentioned disturbances during fasting and hyperglycaemic conditions&#xD;
      using incretin infusions during glucose clamping. Furthermore, stable isotopic tracers will&#xD;
      be used to determine the effect of the incretin hormones on the endogenous glucose handling.&#xD;
&#xD;
      We hypothesise that the effects of the incretin hormones in ESRD will be reduced in respect&#xD;
      to healthy control subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The effect of the incretin hormones on the endocrine pancreatic function in a uremic&#xD;
      environment will be explored during fasting and hyperglycemic conditions in three randomised&#xD;
      examination days.&#xD;
&#xD;
      At a preceding screening day, an oral glucose tolerance test (OGTT) and a dual energy x-ray&#xD;
      absorptiometry (DXA) scan will be performed to determine glucose tolerance and the&#xD;
      distribution of muscle and adipose tissue. The study will be carried out on three separate&#xD;
      days differing with respect to the hormones infused: GLP-1, GIP or placebo (saline) which are&#xD;
      double blinded. The patients will meet from an overnight fast and an infusion of one of the&#xD;
      hormones is initiated. At the same time labeled glucose will be infused to determine the&#xD;
      endogenous hepatic glucose production. A glucose infusion is adjusted according to frequent&#xD;
      plasma glucose measurements to maintain fasting glucose level. After 2 hours a steady state&#xD;
      of the tracer is achieved and a 2 hour hyperglycemic clamp, 3 mmol/l above fasting glucose&#xD;
      concentration will be started. The tracer infusions are continued during the hyperglycemia.&#xD;
      After the 4 hour clamp an arginine bolus will be administered to measure the ability to&#xD;
      increase the secretion of insulin and glucagon.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">April 28, 2016</completion_date>
  <primary_completion_date type="Actual">April 28, 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups</measure>
    <time_frame>Average during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes</time_frame>
    <description>Average plasma insulin concentrations during hyperglycemia</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The effect of GLP-1 and GIP on insulin, glucagon and endogenous glucose production during euglycemia</measure>
    <time_frame>Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes</time_frame>
    <description>Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during euglycemia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of GLP-1 and GIP on early and late phase of insulin, glucagon and endogenous glucose production during hyperglycemia</measure>
    <time_frame>Averages during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes</time_frame>
    <description>Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during the first 10 minutes and last 30 minutes of hyperglycemia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of GLP-1 and GIP on insulin and glucagon response to arginine</measure>
    <time_frame>Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes</time_frame>
    <description>Average plasma insulin and glucagon concentrations 10 minutes following arginine bolus at the end of the examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of GLP-1 and GIP on the peripheral glucose handling</measure>
    <time_frame>Average during the first 4 hours of each examination day. Blood samples are collected at 5-15 minutes interval from time 0 to time 240 minutes</time_frame>
    <description>Average glucose infusion rate during both euglycemia (the first 2 hours) and hyperglycemia (the last 2 hours).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effect of GLP-1 and GIP on potassium concentrations during euglycemia</measure>
    <time_frame>Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes</time_frame>
    <description>Average plasma potassium concentrations during euglycemia</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">24</enrollment>
  <condition>End-stage Renal Disease</condition>
  <arm_group>
    <arm_group_label>End-stage renal disease</arm_group_label>
    <description>Patients with normal glucose tolerance and end-stage renal disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <description>Healthy controls with normal kidney function and normal glucose tolerance</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Eu- and hyperglycemic clamp</intervention_name>
    <description>Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>End-stage renal disease</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Arginine test</intervention_name>
    <description>Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon</description>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_label>End-stage renal disease</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Serum, plasma and urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        1. End-stage renal disease patients receiving chronic hemodialysis treatments&#xD;
&#xD;
          2. Healthy control subjects&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria (End-stage renal disease):&#xD;
&#xD;
          -  Chronic hemodialysis-dependent uremia in more than 3 months&#xD;
&#xD;
        Inclusion Criteria (Healthy controls):&#xD;
&#xD;
          -  Normal kidney function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fasting plasma glucose ≥ 6.1 mmol/l&#xD;
&#xD;
          -  2h plasma glucose ≥ 7.8 after ingestion of 75 grams of glucose&#xD;
&#xD;
          -  Admittance to a hospital&#xD;
&#xD;
          -  Anemia (Hb &lt; 6.0 mmol/l)&#xD;
&#xD;
          -  Ongoing treatment with drugs interfering with glucose metabolism including steroids&#xD;
             and calcineurin inhibitors&#xD;
&#xD;
          -  Bowel resection or any other large abdominal surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Morten B Jørgensen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Nephrology, Rigshospitalet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Nephrology, Rigshospitalet</name>
      <address>
        <city>Copenhagen</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <last_update_submitted>May 19, 2017</last_update_submitted>
  <last_update_submitted_qc>May 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Bo Feldt-Rasmussen</investigator_full_name>
    <investigator_title>MD DMSc</investigator_title>
  </responsible_party>
  <keyword>Incretin hormones</keyword>
  <keyword>End-stage renal disease</keyword>
  <keyword>ESRD</keyword>
  <keyword>GLP-1</keyword>
  <keyword>GIP</keyword>
  <keyword>Insulin</keyword>
  <keyword>Glucagon</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_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/NCT02237521
org study id: H-2-2014-021
nct id: NCT02237521
lead sponsor: 
has dmc: No
Patients with end-stage renal disease (ESRD) have a high prevalence of impaired glucose
      metabolism. The pathophysiological cause is uncertain, but disturbances in the secretion,
      elimination and effect of glucagon, insulin and the two incretin hormones glucagon-like
      peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), probably play
      important roles. Our research group has previously found that dialysis patients without type
      2 diabetes mellitus (T2DM) have a reduced incretin effect and an inability to suppress
      glucagon after a meal - two early pathophysiological characteristics of patients with T2DM
      and normal kidney function.

      The aim of the project is to provide a detailed description of the mechanisms underlying the
      (patho)physiological effects of the incretin hormones in patients with ESRD. We plan to
      investigate the above mentioned disturbances during fasting and hyperglycaemic conditions
      using incretin infusions during glucose clamping. Furthermore, stable isotopic tracers will
      be used to determine the effect of the incretin hormones on the endogenous glucose handling.

      We hypothesise that the effects of the incretin hormones in ESRD will be reduced in respect
      to healthy control subjects.
The effect of the incretin hormones on the endocrine pancreatic function in a uremic
      environment will be explored during fasting and hyperglycemic conditions in three randomised
      examination days.

      At a preceding screening day, an oral glucose tolerance test (OGTT) and a dual energy x-ray
      absorptiometry (DXA) scan will be performed to determine glucose tolerance and the
      distribution of muscle and adipose tissue. The study will be carried out on three separate
      days differing with respect to the hormones infused: GLP-1, GIP or placebo (saline) which are
      double blinded. The patients will meet from an overnight fast and an infusion of one of the
      hormones is initiated. At the same time labeled glucose will be infused to determine the
      endogenous hepatic glucose production. A glucose infusion is adjusted according to frequent
      plasma glucose measurements to maintain fasting glucose level. After 2 hours a steady state
      of the tracer is achieved and a 2 hour hyperglycemic clamp, 3 mmol/l above fasting glucose
      concentration will be started. The tracer infusions are continued during the hyperglycemia.
      After the 4 hour clamp an arginine bolus will be administered to measure the ability to
      increase the secretion of insulin and glucagon.
observational model: Case-Control
time perspective: Cross-Sectional
measure: The effect of GLP-1 and GIP on insulin response during hyperglycemia between groups
time frame: Average during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes
description: Average plasma insulin concentrations during hyperglycemia
measure: The effect of GLP-1 and GIP on insulin, glucagon and endogenous glucose production during euglycemia
time frame: Average during the first 2 hours of each examination day. Blood samples are collected at time 90, 105 and 120 minutes
description: Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during euglycemia.
measure: The effect of GLP-1 and GIP on early and late phase of insulin, glucagon and endogenous glucose production during hyperglycemia
time frame: Averages during the last 2 hours of each examination day. Blood samples are collected at time 122, 124, 126, 130, 210, 225 and 240 minutes
description: Average plasma insulin and glucagon concentrations as well as glucose rate of appearance during the first 10 minutes and last 30 minutes of hyperglycemia.
measure: The effect of GLP-1 and GIP on insulin and glucagon response to arginine
time frame: Average following ariginine bolus. Blood samples are collected at time 242, 244, 246 and 250 minutes
description: Average plasma insulin and glucagon concentrations 10 minutes following arginine bolus at the end of the examination.
measure: The effect of GLP-1 and GIP on the peripheral glucose handling
time frame: Average during the first 4 hours of each examination day. Blood samples are collected at 5-15 minutes interval from time 0 to time 240 minutes
description: Average glucose infusion rate during both euglycemia (the first 2 hours) and hyperglycemia (the last 2 hours).
measure: The effect of GLP-1 and GIP on potassium concentrations during euglycemia
time frame: Average during the first 2 hours of each examination day. Blood samples are collected at time 30, 60, 90 and 120 minutes
description: Average plasma potassium concentrations during euglycemia
arm group label: End-stage renal disease
description: Patients with normal glucose tolerance and end-stage renal disease
arm group label: Controls
description: Healthy controls with normal kidney function and normal glucose tolerance
intervention type: Other
intervention name: Eu- and hyperglycemic clamp
description: Eu- and hyperglycemic clamp with concomitant infusion of the natural occurring hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) or placebo along with stable glucose isotope infusion to measure the effects of the incretins.
arm group label: Controls
arm group label: End-stage renal disease
intervention type: Other
intervention name: Arginine test
description: Bolus infusion of the natural occurring amino acid arginine to measure the ability to increase the secretion of insulin and glucagon
arm group label: Controls
arm group label: End-stage renal disease
Serum, plasma and urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Morten B Jørgensen, MD
role: Principal Investigator
affiliation: Department of Nephrology, Rigshospitalet
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Bo Feldt-Rasmussen
investigator title: MD DMSc
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic