<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/NCT03034226</url>
  </required_header>
  <id_info>
    <org_study_id>Project 1-10-72-304-16</org_study_id>
    <nct_id>NCT03034226</nct_id>
  </id_info>
  <brief_title>Comparison Between Hypoglycemic Counter Regulatory Responses in Type 1 Diabetics vs Control Subjects</brief_title>
  <official_title>A Comparison Between Counter Regulatory Responses in Type 1 Diabetic Patients Versus Healthy Control Subjects With and Without Antecedent Hypoglycemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study compares the hypoglycemic counter regulatory response in type 1 diabetics and in&#xD;
      healthy control subjects with and without antecedent hypoglycemia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Iatrogenic hypoglycemia is one of the main limiting factors for optimal glycemic management&#xD;
      of diabetes. It causes recurrent morbidity in most people with type 1 diabetes and in many&#xD;
      patients with type 2 diabetes and can be fatal. Episodes of hypoglycemia impair&#xD;
      physiologically protective mechanism in subsequent episodes of hypoglycemia. This phenomenon&#xD;
      is known as hypoglycemia-associated autonomic failure (HAAF), the clinical syndromes of&#xD;
      defective glucose counter regulation and hypoglycemia unawareness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 23, 2017</start_date>
  <completion_date type="Actual">January 1, 2019</completion_date>
  <primary_completion_date type="Actual">February 1, 2018</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>9 diabetic subjects and 9 healthy control subjects will be randomized to undergo either first day 1 + day 2 (two consecutive episode of hypoglycemia) or first day 3 + day 4 (one episode of hypoglycemia).</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>Day 2 and day 4 (T=60 minutes - T=240 minutes)</time_frame>
    <description>Insulin sensitivity before, during hypoglycemia and after recovery from hypoglycemia on day 2 (one episode of hypoglycemia) compared with day 4 (two consecutive episodes of hypoglycemia). Insulin sensitivity is measured as M-value derived from the Glucose Infusion Rate (GIR) during a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hormonal counter regulatory response to hypoglycemia</measure>
    <time_frame>Day 2 and day 4 (T=0 minutes, T=30, T=40, T=50, T=120, T=130, T=140, T160, T=170, T=180, T=210, T=220, T=230, T=390, T=400 and T=410</time_frame>
    <description>Hormonal counter regulatory response (epinephrine, norepinephrine, glucagon, cortisol, ghrelin etc.) measured regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms during hypoglycemia</measure>
    <time_frame>Day 2 and day 4 (T=0 minutes - T=420 minutes)</time_frame>
    <description>Using the Edinburgh Hypoglycemia Scale (symptom scale) we will interview the subjects regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Hypoglycemia</condition>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Single episode of hypoglycemia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Day 1: Hyperinsulinemic hypoglycemic clamp 30 min Day 2: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Two episodes of hypoglycemia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Day 3: No intervention (normal blood glucose) Day 4: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Glucose clamp technique</intervention_name>
    <description>Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose</description>
    <arm_group_label>Single episode of hypoglycemia</arm_group_label>
    <arm_group_label>Two episodes of hypoglycemia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Type 1 diabetics&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  More than 5 years of disease duration&#xD;
&#xD;
          -  HbA1c 42-86 mmol/L&#xD;
&#xD;
          -  No known HAAF&#xD;
&#xD;
          -  BMI 22-28&#xD;
&#xD;
          -  Written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Other disease than diabetes f.x epilepsy, ischemic heart disease or heart rhythm&#xD;
             disturbance&#xD;
&#xD;
          -  Medication f.x beta-blockade, steroids, psychotropics&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
        Control subjects&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI 22-28&#xD;
&#xD;
          -  Written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diseases f.x diabetes, epilepsy, ischemic heart disease or heart rhythm disturbance&#xD;
&#xD;
          -  Medication f.x beta-blockade, steroids, psychotropics&#xD;
&#xD;
          -  Smoking&#xD;
&#xD;
          -  Drug abuse&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mads Bisgaard Bengtsen, MD, phd student</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Endocrinology and Internal Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Clinical Medicine</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>January 17, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <last_update_submitted>October 4, 2022</last_update_submitted>
  <last_update_submitted_qc>October 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypoglycemia-Associated Autonomic Failure (HAAF)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemia</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</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/NCT03034226
org study id: Project 1-10-72-304-16
nct id: NCT03034226
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study compares the hypoglycemic counter regulatory response in type 1 diabetics and in
      healthy control subjects with and without antecedent hypoglycemia
Iatrogenic hypoglycemia is one of the main limiting factors for optimal glycemic management
      of diabetes. It causes recurrent morbidity in most people with type 1 diabetes and in many
      patients with type 2 diabetes and can be fatal. Episodes of hypoglycemia impair
      physiologically protective mechanism in subsequent episodes of hypoglycemia. This phenomenon
      is known as hypoglycemia-associated autonomic failure (HAAF), the clinical syndromes of
      defective glucose counter regulation and hypoglycemia unawareness.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: 9 diabetic subjects and 9 healthy control subjects will be randomized to undergo either first day 1 + day 2 (two consecutive episode of hypoglycemia) or first day 3 + day 4 (one episode of hypoglycemia).
primary purpose: Prevention
masking: None (Open Label)
measure: Insulin sensitivity
time frame: Day 2 and day 4 (T=60 minutes - T=240 minutes)
description: Insulin sensitivity before, during hypoglycemia and after recovery from hypoglycemia on day 2 (one episode of hypoglycemia) compared with day 4 (two consecutive episodes of hypoglycemia). Insulin sensitivity is measured as M-value derived from the Glucose Infusion Rate (GIR) during a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp
measure: Hormonal counter regulatory response to hypoglycemia
time frame: Day 2 and day 4 (T=0 minutes, T=30, T=40, T=50, T=120, T=130, T=140, T160, T=170, T=180, T=210, T=220, T=230, T=390, T=400 and T=410
description: Hormonal counter regulatory response (epinephrine, norepinephrine, glucagon, cortisol, ghrelin etc.) measured regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp
measure: Symptoms during hypoglycemia
time frame: Day 2 and day 4 (T=0 minutes - T=420 minutes)
description: Using the Edinburgh Hypoglycemia Scale (symptom scale) we will interview the subjects regularly before, during and after a hyperinsulinemic euglycemic clamp / hyperinsulinemic hypoglycemic clamp
arm group label: Single episode of hypoglycemia
arm group type: Active Comparator
description: Day 1: Hyperinsulinemic hypoglycemic clamp 30 min Day 2: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours
arm group label: Two episodes of hypoglycemia
arm group type: Active Comparator
description: Day 3: No intervention (normal blood glucose) Day 4: Hyperinsulinemic euglycemic clamp and hyperinsulinemic hypoglycemic clamp 7 hours
intervention type: Other
intervention name: Glucose clamp technique
description: Hyperinsulinemic euglycemic and hyperinsulinemic hypoglycemic clamp procedure with infusion of insulin and glucose
arm group label: Single episode of hypoglycemia
arm group label: Two episodes of hypoglycemia
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mads Bisgaard Bengtsen, MD, phd student
role: Principal Investigator
affiliation: Department of Endocrinology and Internal Medicine
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Hypoglycemia
mesh term: Diabetes Mellitus, Type 1
sharing ipd: Undecided