<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/NCT01668485</url>
  </required_header>
  <id_info>
    <org_study_id>T1DM/ITX</org_study_id>
    <nct_id>NCT01668485</nct_id>
  </id_info>
  <brief_title>Mechanisms of Glucose Counterregulation in Pancreatic Islet Transplantation</brief_title>
  <official_title>Metabolic Studies in Type 1 Diabetic Patients After Allogenic Intraportal Islet Transplantation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Giessen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Giessen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pancreatic islet transplantation improves glucose counterregulation and stabilizes glycemic&#xD;
      control in patients with type 1 diabetes mellitus prone to severe hypoglycemia even if&#xD;
      insulin independence is not achieved. However, the extent and underlying metabolic pathways&#xD;
      of this improvement are unknown. Investigators therefore compare systemic glucose turnover&#xD;
      including lactate gluconeogenesis and muscle glucose utilization, between insulin-requiring&#xD;
      islet transplant recipients, matched type 1 diabetic subjects who did not receive islet&#xD;
      transplantation, and matched healthy non-diabetic subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects (n=12 each group) undergo a hypoglycemic and a euglycemic hyperinsulinemic clamp in&#xD;
      a randomized fashion. Systemic and skeletal muscle glucose and lactate kinetics are assessed&#xD;
      using a combination of isotopic and forearm balance techniques.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2001</start_date>
  <completion_date type="Actual">November 2011</completion_date>
  <primary_completion_date type="Actual">November 2010</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Whole body glucose counterregulation</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>Whole body glucose counterregulation is the difference in glucose infusion rates required to maintain the glycemic goal between the hypoglycemic and euglycemic clamp. Clamps were performed at two time points at least two weeks apart. Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systemic glucose release</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>Systemic glucose release is the amount of glucose released primarily from the liver into the blood compartment during a given time. The unit of measure is μmol/kg/min.&#xD;
Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests that will yield this parameter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Skeletal muscle glucose disposal</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>Participants will be followed for the duration of 6-8 weeks to perform the euglycemic and hypoglycemic clamp tests. The unit of measure of this parameters is μmol/kg/min.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gluconeogenesis from lactate</measure>
    <time_frame>6-8 weeks</time_frame>
    <description>This parameter is determined by labelled lactate infused into the proband. The rate of the de novo synthesis of glucose (gluconeogenesis) is determined by the degree of incorporation of the lactate label into glucose molecules. The unit of measure of this parameter is μmol/kg/min.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Islet transplant recipients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hypoglycemic and euglycemic glucose clamp</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Type 1 diabetic subjects</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Hypoglycemic and euglycemic glucose clamp.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-diabetic subjects</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hypoglycemic and euglycemic glucose clamp</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Hypoglycemic and euglycemic glucose clamp</intervention_name>
    <description>Each study participant will be subjected to a continuous infusion of insulin at a rate of 0.8 mU·kg-1·min-1 to induce hypoglycemia (blood glucose 2.8-3 mmol/l) for 30 minutes. At least two weeks later an identical insulin infusion will be administered and euglycemia (blood glucose 5 mmol/l) will be targeted. The order of these interventions will be subject to randomization.</description>
    <arm_group_label>Islet transplant recipients</arm_group_label>
    <arm_group_label>Non-diabetic subjects</arm_group_label>
    <arm_group_label>Type 1 diabetic subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        T1DM/ITX+&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 Diabetes&#xD;
&#xD;
          -  Pancreatic islet transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 2 Diabetes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thomas Linn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Justus Liebig University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Justus Liebig University</name>
      <address>
        <city>Giessen</city>
        <state>Hessia</state>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 13, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <last_update_submitted>August 17, 2012</last_update_submitted>
  <last_update_submitted_qc>August 17, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 21, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Giessen</investigator_affiliation>
    <investigator_full_name>Thomas Linn</investigator_full_name>
    <investigator_title>Professor Dr. med.</investigator_title>
  </responsible_party>
  <keyword>Type 1 diabetes mellitus</keyword>
  <keyword>hypoglycemia counterregulation,</keyword>
  <keyword>pancreatic islet transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemic Agents</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/NCT01668485
org study id: T1DM/ITX
nct id: NCT01668485
lead sponsor: 
has dmc: No
Pancreatic islet transplantation improves glucose counterregulation and stabilizes glycemic
      control in patients with type 1 diabetes mellitus prone to severe hypoglycemia even if
      insulin independence is not achieved. However, the extent and underlying metabolic pathways
      of this improvement are unknown. Investigators therefore compare systemic glucose turnover
      including lactate gluconeogenesis and muscle glucose utilization, between insulin-requiring
      islet transplant recipients, matched type 1 diabetic subjects who did not receive islet
      transplantation, and matched healthy non-diabetic subjects.
Subjects (n=12 each group) undergo a hypoglycemic and a euglycemic hyperinsulinemic clamp in
      a randomized fashion. Systemic and skeletal muscle glucose and lactate kinetics are assessed
      using a combination of isotopic and forearm balance techniques.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Whole body glucose counterregulation
time frame: 6-8 weeks
description: Whole body glucose counterregulation is the difference in glucose infusion rates required to maintain the glycemic goal between the hypoglycemic and euglycemic clamp. Clamps were performed at two time points at least two weeks apart. Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests.
measure: Systemic glucose release
time frame: 6-8 weeks
description: Systemic glucose release is the amount of glucose released primarily from the liver into the blood compartment during a given time. The unit of measure is μmol/kg/min.
Participants will be followed for the duration of 6-8 weeks to perform the hypoglycemic and euglycemic clamp tests that will yield this parameter.
measure: Skeletal muscle glucose disposal
time frame: 6-8 weeks
description: Participants will be followed for the duration of 6-8 weeks to perform the euglycemic and hypoglycemic clamp tests. The unit of measure of this parameters is μmol/kg/min.
measure: Gluconeogenesis from lactate
time frame: 6-8 weeks
description: This parameter is determined by labelled lactate infused into the proband. The rate of the de novo synthesis of glucose (gluconeogenesis) is determined by the degree of incorporation of the lactate label into glucose molecules. The unit of measure of this parameter is μmol/kg/min.
arm group label: Islet transplant recipients
arm group type: Experimental
description: Hypoglycemic and euglycemic glucose clamp
arm group label: Type 1 diabetic subjects
arm group type: Placebo Comparator
description: Hypoglycemic and euglycemic glucose clamp.
arm group label: Non-diabetic subjects
arm group type: Active Comparator
description: Hypoglycemic and euglycemic glucose clamp
intervention type: Procedure
intervention name: Hypoglycemic and euglycemic glucose clamp
description: Each study participant will be subjected to a continuous infusion of insulin at a rate of 0.8 mU·kg-1·min-1 to induce hypoglycemia (blood glucose 2.8-3 mmol/l) for 30 minutes. At least two weeks later an identical insulin infusion will be administered and euglycemia (blood glucose 5 mmol/l) will be targeted. The order of these interventions will be subject to randomization.
arm group label: Islet transplant recipients
arm group label: Non-diabetic subjects
arm group label: Type 1 diabetic subjects
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Thomas Linn, MD
role: Principal Investigator
affiliation: Justus Liebig University
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Giessen
investigator full name: Thomas Linn
investigator title: Professor Dr. med.
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Hypoglycemic Agents