<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/NCT01677104</url>
  </required_header>
  <id_info>
    <org_study_id>11/SW/0195</org_study_id>
    <secondary_id>1204620</secondary_id>
    <nct_id>NCT01677104</nct_id>
  </id_info>
  <brief_title>The Microvascular Function of GLP-1 and Its Analogues</brief_title>
  <official_title>The Microvascular Function of GLP-1 and Its Analogues in Humans, in Vivo: the Role of DPP-IV Inhibition</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Katarina Kos</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Diabetes UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Royal Devon and Exeter NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Incretins have become a successful drug target in the repertoire of medications used for the&#xD;
      treatment of type 2 diabetes. However little is known about a potential benefit of GLP-1 on&#xD;
      the vascular system in humans, independent of their glucose lowering actions and data are&#xD;
      only derived from ex vivo studies in animals. Particularly little is known about clinically&#xD;
      relevant benefits of GLP-1 and its analogues on the microvascular system of individuals with&#xD;
      type 2 diabetes.&#xD;
&#xD;
      The vascular effect could be medicated by endogenous GLP-1 (9,36) amide, the breakdown&#xD;
      product of GLP-1 (7,36) amide which has a low affinity for the GLP-1 receptor. The&#xD;
      investigators hypothesis is that the co-administration of DPP-IV inhibitors will lack the&#xD;
      beneficial effects of GLP-1 on the vascular system as GLP-1 (9,36) amide will not be produced&#xD;
      by the body.&#xD;
&#xD;
      The study aims to examine the response of GLP-1 and its analogues on small blood vessels and&#xD;
      examine the effect of the addition of DPP-IV inhibition in healthy lean individuals, obese&#xD;
      individuals and subjects with Type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>skin blood flow</measure>
    <time_frame>3 hours</time_frame>
    <description>skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">63</enrollment>
  <condition>Type 2 Diabetes</condition>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>DPP-IV inhibitor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Linagliptin 5mg (Tradjenta) before microinjection of GLP-1 and its analogues</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>One placebo tablet before microinjection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GLP-1</intervention_name>
    <description>GLP-1 and its analogues will be compared with placebo with and without prior DPP-IV inhibition</description>
    <arm_group_label>DPP-IV inhibitor</arm_group_label>
    <arm_group_label>Placebo pill</arm_group_label>
    <other_name>native GLP-1(7,36)</other_name>
    <other_name>Exenatide (Byetta)</other_name>
    <other_name>Liraglutide (Vicotza)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>DPP-IV inhibitor</arm_group_label>
    <arm_group_label>Placebo pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Lean BMI ≤ 25.0 kg/m2&#xD;
&#xD;
          -  Obese BMI ≥30.0kg/m2&#xD;
&#xD;
          -  Non diabetic subjects and subjects with Type 2 diabetes on stable medication for at&#xD;
             least 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cardiovascular disease&#xD;
&#xD;
          -  Raynaud's disease&#xD;
&#xD;
          -  current treatment with any anti-hypertensive&#xD;
&#xD;
          -  lipid lowering therapies&#xD;
&#xD;
          -  severe hepatic impairment&#xD;
&#xD;
          -  pregnancy and lactation&#xD;
&#xD;
          -  subjects with Type 2 diabetes on insulin therapy&#xD;
&#xD;
          -  subjects with Type 2 diabetes on sulphonylureas&#xD;
&#xD;
          -  subjects with Type 2 diabetes on incretin based therapies&#xD;
&#xD;
          -  subjects with Type 2 diabetes and peripheral vascular disease&#xD;
&#xD;
          -  subjects with Type 2 diabetes and history of advanced retinopathy&#xD;
&#xD;
          -  subjects with Type 2 diabetes and advanced nephropathy&#xD;
&#xD;
          -  subjects with Type 2 diabetes with uncontrolled diabetes (HbA1c &gt; 8.5%)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Katarina Kos, MD, PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institue of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Diabetes and Vascular Center</name>
      <address>
        <city>Exeter</city>
        <zip>EX2 5AX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>April 12, 2017</last_update_submitted>
  <last_update_submitted_qc>April 12, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Royal Devon and Exeter NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Katarina Kos</investigator_full_name>
    <investigator_title>Consultant Physician and Senior Lecturer</investigator_title>
  </responsible_party>
  <keyword>GLP-1</keyword>
  <keyword>DPP-IV inhibitor</keyword>
  <keyword>microcirculation</keyword>
  <keyword>Exenatide</keyword>
  <keyword>Liraglutide</keyword>
  <keyword>Linagliptin</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liraglutide</mesh_term>
    <mesh_term>Exenatide</mesh_term>
    <mesh_term>Glucagon-Like Peptide 1</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/NCT01677104
org study id: 11/SW/0195
secondary id: 1204620
nct id: NCT01677104
lead sponsor: 
collaborator: 
has dmc: Yes
Incretins have become a successful drug target in the repertoire of medications used for the
      treatment of type 2 diabetes. However little is known about a potential benefit of GLP-1 on
      the vascular system in humans, independent of their glucose lowering actions and data are
      only derived from ex vivo studies in animals. Particularly little is known about clinically
      relevant benefits of GLP-1 and its analogues on the microvascular system of individuals with
      type 2 diabetes.

      The vascular effect could be medicated by endogenous GLP-1 (9,36) amide, the breakdown
      product of GLP-1 (7,36) amide which has a low affinity for the GLP-1 receptor. The
      investigators hypothesis is that the co-administration of DPP-IV inhibitors will lack the
      beneficial effects of GLP-1 on the vascular system as GLP-1 (9,36) amide will not be produced
      by the body.

      The study aims to examine the response of GLP-1 and its analogues on small blood vessels and
      examine the effect of the addition of DPP-IV inhibition in healthy lean individuals, obese
      individuals and subjects with Type 2 diabetes.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: skin blood flow
time frame: 3 hours
description: skin blood flow will be assessed before and after microinjection of GLP-1 or its analogues and the injection site monitored and compared to sites injected with placebo
arm group label: DPP-IV inhibitor
arm group type: Active Comparator
description: Linagliptin 5mg (Tradjenta) before microinjection of GLP-1 and its analogues
arm group label: Placebo pill
arm group type: Placebo Comparator
description: One placebo tablet before microinjection
intervention type: Drug
intervention name: GLP-1
description: GLP-1 and its analogues will be compared with placebo with and without prior DPP-IV inhibition
arm group label: DPP-IV inhibitor
arm group label: Placebo pill
other name: native GLP-1(7,36)
other name: Exenatide (Byetta)
other name: Liraglutide (Vicotza)
intervention type: Drug
intervention name: Placebo
arm group label: DPP-IV inhibitor
arm group label: Placebo pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Katarina Kos, MD, PHD
role: Principal Investigator
affiliation: Institue of Biomedical and Clinical Sciences, Peninsula Medical School, University of Exeter
facility: 
country: United Kingdom
responsible party type: Sponsor-Investigator
investigator affiliation: Royal Devon and Exeter NHS Foundation Trust
investigator full name: Katarina Kos
investigator title: Consultant Physician and Senior Lecturer
mesh term: Liraglutide
mesh term: Exenatide
mesh term: Glucagon-Like Peptide 1