<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/NCT03835013</url>
  </required_header>
  <id_info>
    <org_study_id>COCOA</org_study_id>
    <secondary_id>18/EM/0417</secondary_id>
    <secondary_id>250402</secondary_id>
    <nct_id>NCT03835013</nct_id>
  </id_info>
  <brief_title>Haemodynamic Effects of GLP-1 and Glucagon in Healthy Male Volunteers</brief_title>
  <acronym>COCOA</acronym>
  <official_title>A Comparison of the Haemodynamic and Metabolic Effects of Intravenous Glucagon-like Peptide-1, Glucagon and Glucagon-like Peptide-1:Glucagon Co-agonism in Healthy Male Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cambridge University Hospitals NHS Foundation Trust</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>
      The study seeks to explore the cardiovascular effects of co-agonism at two peptide receptors,&#xD;
      GLP-1 and glucagon. Glucagon, exenatide and 0.9% saline will be intravenously infused, both&#xD;
      in isolation, and combination into healthy male participants. Overall, the aim of the study&#xD;
      is to further our understanding on the role these endogenous substances play (both in&#xD;
      isolation and combination) in haemodynamic regulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Co-agonist peptides (such as at the GLP-1:glucagon receptor) are currently in clinical&#xD;
      development for type 2 diabetes with the dual intention of reducing body weight and&#xD;
      controlling blood glucose. However, there is a lack of data on the effects that co-agonism&#xD;
      has on haemodynamic regulation.&#xD;
&#xD;
      Part A - Healthy male participants, by acting as their own control, will attend for two&#xD;
      intravenous infusion visits (combination of 0.9% saline and glucagon). These will occur in a&#xD;
      predefined but random order so that participants will be blinded to the infusion they are&#xD;
      receiving. Each infusion visit will comprise of 15 minute baseline followed by a 120 minute&#xD;
      infusion. Detailed non-invasive cardiovascular measurements (including peripheral/central&#xD;
      blood pressure, heart rate, stroke volume, heart rate variability) and bloods (including&#xD;
      insulin, glucose, GLP-1, glucagon) will be collected as part of the study. It was previously&#xD;
      planned that GLP-1 7-36 amide 0.6pmol/kg/min and 1.2pmol/kg/min would be infused for Part A&#xD;
      resulting in 5 infusions (rather than current 2 infusions). However due to supply/technical&#xD;
      issues this was not possible and therefore exenatide (GLP-1 receptor agonist) shall be used&#xD;
      in Part B.&#xD;
&#xD;
      Part B - Healthy male participants, by acting as their own control, will attend for four&#xD;
      intravenous infusion visits (combination of 0.9% saline, glucagon, exenatide). These will&#xD;
      occur in a predefined but random order so that participants will be blinded to the infusion&#xD;
      they are receiving. Each infusion visit will comprise of 15 minute baseline followed by a 60&#xD;
      minute infusion. Detailed non-invasive cardiovascular measurements (including&#xD;
      peripheral/central blood pressure, heart rate, stroke volume, heart rate variability) and&#xD;
      bloods (including insulin, glucose, GLP-1, glucagon) will be collected as part of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 11, 2019</start_date>
  <completion_date type="Anticipated">July 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2022</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Part A - 2 infusions Part B - 4 infusions</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Heart rate (bpm)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Brachial systolic and diastolic blood pressure (mmHg)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Central systolic and diastolic blood pressure and mean arterial pressure (mmHg) measured with SphygmoCor XCEL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Stroke volume (ml) measured by bioimpedance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Cardiac output (L/min) measured by bioimpedance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>peripheral vascular resistance (dynes/sec/cm)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Heart rate variability (normalised low frequency, LF, high frequency, HF and LF/HF ratio)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-5 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Glucose, in mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>C-peptide, in pmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Glucagon, in pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Insulin, in pmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Free fatty acids, in μmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Total GLP-1 and total active GLP-1, in pg/ml</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.</measure>
    <time_frame>Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks</time_frame>
    <description>Gastric inhibitory polypeptide, in pg/ml</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>Part A - Infusion A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>60 minute intravenous infusion of 0.9% saline&#xD;
Followed by:&#xD;
60 minute intravenous infusion of 0.9% saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A - Infusion B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>60 minute intravenous infusion of glucagon 25ng/kg/min and 0.9% saline.&#xD;
Followed by:&#xD;
60 minute infusion of glucagon 50ng/kg/min and 0.9% saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B - Infusion A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A 60 minute intravenous infusion of 0.9% saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B - Infusion B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes followed by 25ng/min) and 0.9% saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B - Infusion C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A 60 minute intravenous infusion of glucagon (25ng/kg/min) and 0.9% saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B - Infusion D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes then 25ng/min) and glucagon (25ng/kg/min)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline 0.9%</intervention_name>
    <description>Intravenous infusion of 0.9% saline</description>
    <arm_group_label>Part A - Infusion A</arm_group_label>
    <arm_group_label>Part A - Infusion B</arm_group_label>
    <arm_group_label>Part B - Infusion A</arm_group_label>
    <arm_group_label>Part B - Infusion B</arm_group_label>
    <arm_group_label>Part B - Infusion C</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glucagon (25ng/kg/min)</intervention_name>
    <description>Intravenous infusion of glucagon 25ng/kg/min</description>
    <arm_group_label>Part A - Infusion B</arm_group_label>
    <arm_group_label>Part B - Infusion C</arm_group_label>
    <arm_group_label>Part B - Infusion D</arm_group_label>
    <other_name>Glucagon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glucagon (50ng/kg/min)</intervention_name>
    <description>Intravenous infusion of glucagon 50ng/kg/min</description>
    <arm_group_label>Part A - Infusion B</arm_group_label>
    <other_name>Glucagon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide</intervention_name>
    <description>Intravenous infusion of Exenatide (loading 50ng/min for 30 minutes followed by 25ng/min for 30 minutes</description>
    <arm_group_label>Part B - Infusion B</arm_group_label>
    <arm_group_label>Part B - Infusion D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent to participate&#xD;
&#xD;
          -  Aged 18 to 40&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Current non-smoker&#xD;
&#xD;
          -  BMI &gt;18.0 and &lt;30kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female&#xD;
&#xD;
          -  Sustained Hypertension (sustained BP &gt;160/100mmHg) or hypotension (systolic BP below&#xD;
             90 mmHg)&#xD;
&#xD;
          -  Clinically significant heart disease&#xD;
&#xD;
          -  Implanted heart pace-maker or implantable cardioverter defibrillator (ICD)&#xD;
&#xD;
          -  Known active malignancy&#xD;
&#xD;
          -  Known renal failure (creatinine &gt;140μmol/L)&#xD;
&#xD;
          -  Known diabetes mellitus (type 1 or 2)&#xD;
&#xD;
          -  Use of vasoactive medications or NSAIDS/aspirin within 24 hours of study visits&#xD;
&#xD;
          -  Use of formal anticoagulant therapy such as, but not limited to, heparin, warfarin or&#xD;
             rivaroxaban&#xD;
&#xD;
          -  Current involvement in the active treatment phase of other research studies,&#xD;
             (excluding observations/noninterventional)&#xD;
&#xD;
          -  Any other clinical reason which may preclude entry in the opinion of the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ian Wilkinson, MA DM FRCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>James Goodman, MD</last_name>
    <phone>01223 336806</phone>
    <phone_ext>+44</phone_ext>
    <email>jdhg3@medschl.cam.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Addenbrooke's Hospital</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James Goodman, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>January 25, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>December 10, 2021</last_update_submitted>
  <last_update_submitted_qc>December 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Dr Ian B Wilkinson</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Exenatide</mesh_term>
    <mesh_term>Glucagon</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/NCT03835013
org study id: COCOA
secondary id: 18/EM/0417
secondary id: 250402
nct id: NCT03835013
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study seeks to explore the cardiovascular effects of co-agonism at two peptide receptors,
      GLP-1 and glucagon. Glucagon, exenatide and 0.9% saline will be intravenously infused, both
      in isolation, and combination into healthy male participants. Overall, the aim of the study
      is to further our understanding on the role these endogenous substances play (both in
      isolation and combination) in haemodynamic regulation.
Co-agonist peptides (such as at the GLP-1:glucagon receptor) are currently in clinical
      development for type 2 diabetes with the dual intention of reducing body weight and
      controlling blood glucose. However, there is a lack of data on the effects that co-agonism
      has on haemodynamic regulation.

      Part A - Healthy male participants, by acting as their own control, will attend for two
      intravenous infusion visits (combination of 0.9% saline and glucagon). These will occur in a
      predefined but random order so that participants will be blinded to the infusion they are
      receiving. Each infusion visit will comprise of 15 minute baseline followed by a 120 minute
      infusion. Detailed non-invasive cardiovascular measurements (including peripheral/central
      blood pressure, heart rate, stroke volume, heart rate variability) and bloods (including
      insulin, glucose, GLP-1, glucagon) will be collected as part of the study. It was previously
      planned that GLP-1 7-36 amide 0.6pmol/kg/min and 1.2pmol/kg/min would be infused for Part A
      resulting in 5 infusions (rather than current 2 infusions). However due to supply/technical
      issues this was not possible and therefore exenatide (GLP-1 receptor agonist) shall be used
      in Part B.

      Part B - Healthy male participants, by acting as their own control, will attend for four
      intravenous infusion visits (combination of 0.9% saline, glucagon, exenatide). These will
      occur in a predefined but random order so that participants will be blinded to the infusion
      they are receiving. Each infusion visit will comprise of 15 minute baseline followed by a 60
      minute infusion. Detailed non-invasive cardiovascular measurements (including
      peripheral/central blood pressure, heart rate, stroke volume, heart rate variability) and
      bloods (including insulin, glucose, GLP-1, glucagon) will be collected as part of the study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Part A - 2 infusions Part B - 4 infusions
primary purpose: Basic Science
masking: Single (Participant)
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Heart rate (bpm)
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Brachial systolic and diastolic blood pressure (mmHg)
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Central systolic and diastolic blood pressure and mean arterial pressure (mmHg) measured with SphygmoCor XCEL
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Stroke volume (ml) measured by bioimpedance
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Cardiac output (L/min) measured by bioimpedance
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: peripheral vascular resistance (dynes/sec/cm)
measure: Changes in haemodynamic parameters following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Heart rate variability (normalised low frequency, LF, high frequency, HF and LF/HF ratio)
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-5 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Glucose, in mmol/L
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: C-peptide, in pmol/L
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Glucagon, in pg/ml
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Insulin, in pmol/L
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Free fatty acids, in μmol/L
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Total GLP-1 and total active GLP-1, in pg/ml
measure: Changes in glucose homeostasis following intravenous infusion of 0.9% saline, glucagon, exenatide and their combination.
time frame: Comparison between 2 hour infusion visit 1-2 (Part A) / 1 hour infusion visit 1-4 (Part B), over a maximum period of 15 weeks
description: Gastric inhibitory polypeptide, in pg/ml
arm group label: Part A - Infusion A
arm group type: Placebo Comparator
description: 60 minute intravenous infusion of 0.9% saline
Followed by:
60 minute intravenous infusion of 0.9% saline
arm group label: Part A - Infusion B
arm group type: Active Comparator
description: 60 minute intravenous infusion of glucagon 25ng/kg/min and 0.9% saline.
Followed by:
60 minute infusion of glucagon 50ng/kg/min and 0.9% saline
arm group label: Part B - Infusion A
arm group type: Active Comparator
description: A 60 minute intravenous infusion of 0.9% saline
arm group label: Part B - Infusion B
arm group type: Active Comparator
description: A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes followed by 25ng/min) and 0.9% saline
arm group label: Part B - Infusion C
arm group type: Active Comparator
description: A 60 minute intravenous infusion of glucagon (25ng/kg/min) and 0.9% saline
arm group label: Part B - Infusion D
arm group type: Active Comparator
description: A 60 minute intravenous infusion of exenatide (50ng/min for 30 minutes then 25ng/min) and glucagon (25ng/kg/min)
intervention type: Drug
intervention name: Saline 0.9%
description: Intravenous infusion of 0.9% saline
arm group label: Part A - Infusion A
arm group label: Part A - Infusion B
arm group label: Part B - Infusion A
arm group label: Part B - Infusion B
arm group label: Part B - Infusion C
other name: Placebo
intervention type: Drug
intervention name: Glucagon (25ng/kg/min)
description: Intravenous infusion of glucagon 25ng/kg/min
arm group label: Part A - Infusion B
arm group label: Part B - Infusion C
arm group label: Part B - Infusion D
other name: Glucagon
intervention type: Drug
intervention name: Glucagon (50ng/kg/min)
description: Intravenous infusion of glucagon 50ng/kg/min
arm group label: Part A - Infusion B
other name: Glucagon
intervention type: Drug
intervention name: Exenatide
description: Intravenous infusion of Exenatide (loading 50ng/min for 30 minutes followed by 25ng/min for 30 minutes
arm group label: Part B - Infusion B
arm group label: Part B - Infusion D
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ian Wilkinson, MA DM FRCP
role: Principal Investigator
affiliation: University of Cambridge
last name: James Goodman, MD
phone: 01223 336806
phone ext: +44
email: jdhg3@medschl.cam.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
investigator full name: Dr Ian B Wilkinson
investigator title: Principal Investigator
mesh term: Cardiovascular Diseases
mesh term: Exenatide
mesh term: Glucagon
mesh term: Glucagon-Like Peptide 1