<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/NCT02232971</url>
  </required_header>
  <id_info>
    <org_study_id>GluST1_2014</org_study_id>
    <secondary_id>2014-002267-15</secondary_id>
    <secondary_id>H-1-2014-041</secondary_id>
    <nct_id>NCT02232971</nct_id>
  </id_info>
  <brief_title>Treatment of Low Blood Sugar With Glucagon Among Patients With Type 1 Diabetes</brief_title>
  <acronym>GluST1</acronym>
  <official_title>Treatment of Hypoglycemia With Glucagon Among Patients With Type 1 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Novo Nordic Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hvidovre University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Patients with type 1 diabetes (T1D) need a lifelong supply of external insulin&#xD;
      and are advised to aim for near-normalization of blood glucose levels through intensive&#xD;
      insulin therapy. We propose a new approach for achieving treatment goals in T1D: the combined&#xD;
      use of insulin and glucagon, i.e. dual-hormone treatment.Only recently the prospect of&#xD;
      treating patients with soluble glucagon has arisen and thus studies of low dose glucagon&#xD;
      treatment of mild hypoglycemia are needed to determine whether there is clinical rationale&#xD;
      for dual-hormone treatment of T1D.&#xD;
&#xD;
      Aim: The purpose of this clinical study is to investigate the glycemic response to&#xD;
      subcutaneous glucagon administration during mild hypoglycemia in T1D patients treated with&#xD;
      insulin pump. Different glucagon doses are applied to determine the most appropriate dose for&#xD;
      future dual-hormone treatment of T1D.&#xD;
&#xD;
      Methods: A clinical, randomized, single blinded, crossover study will be conducted. Eight T1D&#xD;
      patients treated with insulin pump are studied on four days. All patients are in good&#xD;
      metabolic control (HbA1c &lt; 7.5%), C-peptide negative and with hypoglycemia awareness. On each&#xD;
      study day, hypoglycemia is induced with subcutaneously insulin and afterward treated with a&#xD;
      single subcutaneous dose of glucagon. The study procedures are identical on all days except&#xD;
      from the administered dose of glucagon (day 1: placebo, day 2: 100 ug, day 3: 200 ug, day 4:&#xD;
      300 ug). All patients are blinded for the glucagon dose and carry out the four days in random&#xD;
      order.&#xD;
&#xD;
      Endpoints: The present study focuses primarily on the dose related plasma glucose response of&#xD;
      glucagon; secondary on the duration of the hyperglycemic effect of glucagon and tertiary the&#xD;
      glucagon effect on catecholamine, cortisol, growth hormone, free fatty acids and&#xD;
      triglycerides.&#xD;
&#xD;
      The study will be conducted from august 2014.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">July 2015</completion_date>
  <primary_completion_date type="Actual">January 2015</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>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum plasma glucose response</measure>
    <time_frame>Plasma glucose measured every five minutes after administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of hyperglycemic effect of glucagon</measure>
    <time_frame>Plasma glucose is measured every five minutes. Time period is two -three hours after glucagon administration</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma Catecholamine</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma free fatty acids</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Beta-Hydroxybutyric acid</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Plasma Glucagon</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Serum Growth hormone</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Serum Cortisol</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Serum Insulin (Novorapid)</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Adverse reaction: Stomach pain</measure>
    <time_frame>One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.</time_frame>
    <description>Visual analog scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Adverse reaction: Headache</measure>
    <time_frame>One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.</time_frame>
    <description>Visual Analog scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Adverse Reaction: Vertigo</measure>
    <time_frame>One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.</time_frame>
    <description>Visual analog scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Adverse reaction: Nausea</measure>
    <time_frame>One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.</time_frame>
    <description>Visual analog scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Adverse reaction: Hunger</measure>
    <time_frame>One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.</time_frame>
    <description>Visual analog scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Plasma triglycerides</measure>
    <time_frame>Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration</time_frame>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">8</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Isotonic Saline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glucagon 0.1 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GlucaGen(r) 0.1 mg administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glucagon 0.2 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GlucaGen(r) 0.2 mg administration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glucagon 0.3 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GlucaGen(r) 0.3 mg administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glucagon</intervention_name>
    <description>Glucagon is given in three different doses according to three research days.</description>
    <arm_group_label>Glucagon 0.1 mg</arm_group_label>
    <arm_group_label>Glucagon 0.2 mg</arm_group_label>
    <arm_group_label>Glucagon 0.3 mg</arm_group_label>
    <other_name>GlucaGen (r)</other_name>
    <other_name>Disp. no. 2514</other_name>
    <other_name>Novo Nordisk A/S</other_name>
    <other_name>Novo Allé</other_name>
    <other_name>2880 Bagsværd</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Isotonic saline solution</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Natriumklorid isotonisk &quot;SAD&quot;</other_name>
    <other_name>D.sp.no. 6733</other_name>
    <other_name>Amgros I/S</other_name>
    <other_name>Dampfærgevej 22</other_name>
    <other_name>Postbox 2593</other_name>
    <other_name>2100 København Ø</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females aged 18-65 years&#xD;
&#xD;
          -  Diagnosed with type 1 diabetes &gt; 3 years&#xD;
&#xD;
          -  HbA1c &lt; 58 mmol/mol&#xD;
&#xD;
          -  No appearance of autonome neuropathy&#xD;
&#xD;
          -  Body mass index (BMI) between 20-25 kg/m2&#xD;
&#xD;
          -  Remained hypoglycemic awareness&#xD;
&#xD;
          -  Insulin pump treatment &gt; 1 year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergic to glucagon or lactose&#xD;
&#xD;
          -  Pregnancy, breast-feeding, intention of becoming pregnant, or not using adequate&#xD;
             contraception&#xD;
&#xD;
          -  Any disease or condition which would interfere with the subject's safety&#xD;
&#xD;
          -  Use of a medication that significantly impacts glucose metabolism&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ajenthen Ranjan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hvidovre University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Signe Schmidt, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Hvidovre University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kirsten Nørgaard, MD, DMSc</last_name>
    <role>Study Chair</role>
    <affiliation>Hvidovre University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sten Madsbad, Prof, DMSc</last_name>
    <role>Study Chair</role>
    <affiliation>Hvidovre University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jens J Holst, Prof, DMSc</last_name>
    <role>Study Chair</role>
    <affiliation>University of Copenhagen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hvidovre University Hospital</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <link>
    <url>http://www.diacongroup.org/</url>
    <description>DiaCon group focuses on developing new technologies for treatment of type 1 diabetes</description>
  </link>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>August 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <last_update_submitted>March 24, 2015</last_update_submitted>
  <last_update_submitted_qc>March 24, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 25, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hvidovre University Hospital</investigator_affiliation>
    <investigator_full_name>Ajenthen Ranjan</investigator_full_name>
    <investigator_title>MD, PhD student</investigator_title>
  </responsible_party>
  <keyword>glucagon</keyword>
  <keyword>insulin pump</keyword>
  <keyword>artificial pancreas</keyword>
  <keyword>closed-loop</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>Glucagon</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/NCT02232971
org study id: GluST1_2014
secondary id: 2014-002267-15
secondary id: H-1-2014-041
nct id: NCT02232971
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Background: Patients with type 1 diabetes (T1D) need a lifelong supply of external insulin
      and are advised to aim for near-normalization of blood glucose levels through intensive
      insulin therapy. We propose a new approach for achieving treatment goals in T1D: the combined
      use of insulin and glucagon, i.e. dual-hormone treatment.Only recently the prospect of
      treating patients with soluble glucagon has arisen and thus studies of low dose glucagon
      treatment of mild hypoglycemia are needed to determine whether there is clinical rationale
      for dual-hormone treatment of T1D.

      Aim: The purpose of this clinical study is to investigate the glycemic response to
      subcutaneous glucagon administration during mild hypoglycemia in T1D patients treated with
      insulin pump. Different glucagon doses are applied to determine the most appropriate dose for
      future dual-hormone treatment of T1D.

      Methods: A clinical, randomized, single blinded, crossover study will be conducted. Eight T1D
      patients treated with insulin pump are studied on four days. All patients are in good
      metabolic control (HbA1c < 7.5%), C-peptide negative and with hypoglycemia awareness. On each
      study day, hypoglycemia is induced with subcutaneously insulin and afterward treated with a
      single subcutaneous dose of glucagon. The study procedures are identical on all days except
      from the administered dose of glucagon (day 1: placebo, day 2: 100 ug, day 3: 200 ug, day 4:
      300 ug). All patients are blinded for the glucagon dose and carry out the four days in random
      order.

      Endpoints: The present study focuses primarily on the dose related plasma glucose response of
      glucagon; secondary on the duration of the hyperglycemic effect of glucagon and tertiary the
      glucagon effect on catecholamine, cortisol, growth hormone, free fatty acids and
      triglycerides.

      The study will be conducted from august 2014.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Maximum plasma glucose response
time frame: Plasma glucose measured every five minutes after administration
measure: Duration of hyperglycemic effect of glucagon
time frame: Plasma glucose is measured every five minutes. Time period is two -three hours after glucagon administration
measure: Plasma Catecholamine
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Plasma free fatty acids
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Plasma Beta-Hydroxybutyric acid
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Plasma Glucagon
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Serum Growth hormone
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Serum Cortisol
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Serum Insulin (Novorapid)
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Adverse reaction: Stomach pain
time frame: One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
description: Visual analog scale
measure: Adverse reaction: Headache
time frame: One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
description: Visual Analog scale
measure: Adverse Reaction: Vertigo
time frame: One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
description: Visual analog scale
measure: Adverse reaction: Nausea
time frame: One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
description: Visual analog scale
measure: Adverse reaction: Hunger
time frame: One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
description: Visual analog scale
measure: Plasma triglycerides
time frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
arm group label: Placebo
arm group type: Placebo Comparator
description: Isotonic Saline
arm group label: Glucagon 0.1 mg
arm group type: Experimental
description: GlucaGen(r) 0.1 mg administration
arm group label: Glucagon 0.2 mg
arm group type: Experimental
description: GlucaGen(r) 0.2 mg administration
arm group label: Glucagon 0.3 mg
arm group type: Experimental
description: GlucaGen(r) 0.3 mg administration
intervention type: Drug
intervention name: Glucagon
description: Glucagon is given in three different doses according to three research days.
arm group label: Glucagon 0.1 mg
arm group label: Glucagon 0.2 mg
arm group label: Glucagon 0.3 mg
other name: GlucaGen (r)
other name: Disp. no. 2514
other name: Novo Nordisk A/S
other name: Novo Allé
other name: 2880 Bagsværd
intervention type: Other
intervention name: Isotonic saline solution
description: Placebo
arm group label: Placebo
other name: Natriumklorid isotonisk "SAD"
other name: D.sp.no. 6733
other name: Amgros I/S
other name: Dampfærgevej 22
other name: Postbox 2593
other name: 2100 København Ø
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ajenthen Ranjan, MD
role: Principal Investigator
affiliation: Hvidovre University Hospital
last name: Signe Schmidt, MD, PhD
role: Study Director
affiliation: Hvidovre University Hospital
last name: Kirsten Nørgaard, MD, DMSc
role: Study Chair
affiliation: Hvidovre University Hospital
last name: Sten Madsbad, Prof, DMSc
role: Study Chair
affiliation: Hvidovre University Hospital
last name: Jens J Holst, Prof, DMSc
role: Study Chair
affiliation: University of Copenhagen
facility: 
country: Denmark
url: http://www.diacongroup.org/
description: DiaCon group focuses on developing new technologies for treatment of type 1 diabetes
responsible party type: Principal Investigator
investigator affiliation: Hvidovre University Hospital
investigator full name: Ajenthen Ranjan
investigator title: MD, PhD student
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Glucagon