<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/NCT03017352</url>
  </required_header>
  <id_info>
    <org_study_id>Eudract-nr.: 2016-001365-92</org_study_id>
    <nct_id>NCT03017352</nct_id>
  </id_info>
  <brief_title>Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases</brief_title>
  <acronym>MAG1C</acronym>
  <official_title>Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases: A Randomised, Placebo-controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Filip Krag Knop</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Steno Diabetes Center Copenhagen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Gentofte, Copenhagen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with type 1 diabetes (T1D) depend on insulin therapy as substitution for the lack of&#xD;
      endocrine insulin production due to an autoimmune destruction of beta-cells in the pancreatic&#xD;
      inslets. Insulin therapy is based on long lasting basal insulin for controlling fasting&#xD;
      plasma glucose, and short lasting mealtime insulin for the postprandial plasma glucose. The&#xD;
      long term efficacy of this treatment is measured in glycated haemoglobin A1c (HbA1c) of &lt;7.0%&#xD;
      as the treatment goal.&#xD;
&#xD;
      Intensive insulin therapy is associated with side effects such as hypoglycaemia, weight gain,&#xD;
      and unwanted exaggerated excursions in PPG. This may ultimately affect treatment compliance.&#xD;
&#xD;
      The abovementioned problems associated with insulin treatment in T1D can also be seen in&#xD;
      insulin-treated patients with type 2 diabetes (T2D). However, in T2D the combination of&#xD;
      insulin with glucagon-like peptide-1 (GLP-1) receptor agonist (RA) has proven effective in&#xD;
      reducing the weight gain and insulin dose in insulin-treated patients with T2D without&#xD;
      exacerbating the risk of hypoglycaemia.&#xD;
&#xD;
      Exenatid is a short lasting GLP-1RA approved for treatment in T2D, and the investigators&#xD;
      intend to evaluate it in a randomized, controlled trial as add-on therapy to standard insulin&#xD;
      therapy for patients with T1D.&#xD;
&#xD;
      The investigators hypothesise that the add-on of exenatide to insulin therapy in patients&#xD;
      with T1D will reduce insulin requirements, glycaemic excursions and body weight and improve&#xD;
      glycaemic control without increasing the risk of hypoglycaemia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">June 2019</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HbA1c</measure>
    <time_frame>6 months</time_frame>
    <description>Change in HbA1c from baseline to end of study (time 6 months)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>adverse events (including hypoglycaemic episodes)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in insulin dosage</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in body weight</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in BMI</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in body composition</measure>
    <time_frame>6 months</time_frame>
    <description>DXA scan measuring bonemineral density</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in body composition</measure>
    <time_frame>6 months</time_frame>
    <description>DXA scan measuring lean mass</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in body composition</measure>
    <time_frame>6 months</time_frame>
    <description>DXA scan measuring fat mass</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in fasting plasma glucose</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in post prandial plasma glucose</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>changes in fasting plasma levels of C-peptide</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life self reported</measure>
    <time_frame>6 months</time_frame>
    <description>Quality of Life Questionaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment satisfaction</measure>
    <time_frame>6 months</time_frame>
    <description>Diabetes treatment satisfactory questionnaire status version</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment satisfaction</measure>
    <time_frame>6 months</time_frame>
    <description>Diabetes treatment satisfactory questionnaire change version</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>dietary patterns</measure>
    <time_frame>6 months</time_frame>
    <description>Food frequency questionaire three times during the intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL (High Density Lipoprotein)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LDL (Low Density Lipoprotein)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VLDL (Very Low Density Lipoprotein)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total cholesterol</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>triglycerides</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proBNP (Pro-Brain Natriuretic Peptide)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hsCRP (High-Sensitivity C-Reactive Protein)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">108</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Exenatide 10 mikrogram, thrice daily, subcutaneous injection prior to main meals, 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, thrice daily, subcutaneous injection prior to main meals, 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exenatide</intervention_name>
    <arm_group_label>Intervention</arm_group_label>
    <other_name>Byetta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  T1D according to WHO criteria with duration of ≥1 year&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  BMI &gt;22.0 kg/m2&#xD;
&#xD;
          -  HbA1c &gt;7.5% and &lt;10.0% at visit 0 (screening)&#xD;
&#xD;
          -  Able to count carbohydrates&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Insulin pump treatment&#xD;
&#xD;
          -  Hypoglycaemia unawareness (inability to register low blood glucose)&#xD;
&#xD;
          -  Diabetic gastroparesis&#xD;
&#xD;
          -  Compromised kidney function (eGFR &lt;60 ml/min/1.73m2, dialysis or kidney&#xD;
             transplantation)&#xD;
&#xD;
          -  Liver disease with elevated plasma alanine aminotransferase (ALT) &gt; three times the&#xD;
             upper limit of normal (measured at visit 0 with the possibility of one repeat analysis&#xD;
             within a week, and the last measured value as being conclusive)&#xD;
&#xD;
          -  History of acute and/or chronic pancreatitis&#xD;
&#xD;
          -  Subjects with personal or family history of medullary carcinoma or MEN syndrome&#xD;
&#xD;
          -  Inflammatory bowel disease&#xD;
&#xD;
          -  Cancer unless in complete remission for &gt;5 years&#xD;
&#xD;
          -  Proliferative retinopathy&#xD;
&#xD;
          -  Other concomitant disease or treatment that according to the investigator's assessment&#xD;
             makes the patient unsuitable for study participation&#xD;
&#xD;
          -  Alcohol/drug abuse&#xD;
&#xD;
          -  Fertile women not using chemical (tablet/pill, depot injection of progesterone,&#xD;
             subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch)&#xD;
             or mechanical (spirals) contraceptives&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Known or suspected hypersensitivity to trial product or related products&#xD;
&#xD;
          -  Receipt of an investigational drug within 30 days prior to visit 0&#xD;
&#xD;
          -  Simultaneous participation in any other clinical intervention trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Steno Diabetes Center Copenhagen</name>
      <address>
        <city>Gentofte</city>
        <state>Capital Region</state>
        <zip>2820</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>Johansen NJ, Dejgaard TF, Lund A, Vilsboll T, Andersen HU, Knop FK. Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial. BMJ Open. 2018 Jun 27;8(6):e021861. doi: 10.1136/bmjopen-2018-021861.</citation>
    <PMID>29950475</PMID>
  </reference>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>July 9, 2019</last_update_submitted>
  <last_update_submitted_qc>July 9, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Gentofte, Copenhagen</investigator_affiliation>
    <investigator_full_name>Filip Krag Knop</investigator_full_name>
    <investigator_title>Professor, MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Diabetes Mellitus, Type 1</keyword>
  <keyword>Exenatide</keyword>
  <keyword>Incretins</keyword>
  <keyword>GLP-1</keyword>
  <keyword>Insulin</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>Exenatide</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/NCT03017352
org study id: Eudract-nr.: 2016-001365-92
nct id: NCT03017352
lead sponsor: 
collaborator: 
has dmc: Yes
Patients with type 1 diabetes (T1D) depend on insulin therapy as substitution for the lack of
      endocrine insulin production due to an autoimmune destruction of beta-cells in the pancreatic
      inslets. Insulin therapy is based on long lasting basal insulin for controlling fasting
      plasma glucose, and short lasting mealtime insulin for the postprandial plasma glucose. The
      long term efficacy of this treatment is measured in glycated haemoglobin A1c (HbA1c) of <7.0%
      as the treatment goal.

      Intensive insulin therapy is associated with side effects such as hypoglycaemia, weight gain,
      and unwanted exaggerated excursions in PPG. This may ultimately affect treatment compliance.

      The abovementioned problems associated with insulin treatment in T1D can also be seen in
      insulin-treated patients with type 2 diabetes (T2D). However, in T2D the combination of
      insulin with glucagon-like peptide-1 (GLP-1) receptor agonist (RA) has proven effective in
      reducing the weight gain and insulin dose in insulin-treated patients with T2D without
      exacerbating the risk of hypoglycaemia.

      Exenatid is a short lasting GLP-1RA approved for treatment in T2D, and the investigators
      intend to evaluate it in a randomized, controlled trial as add-on therapy to standard insulin
      therapy for patients with T1D.

      The investigators hypothesise that the add-on of exenatide to insulin therapy in patients
      with T1D will reduce insulin requirements, glycaemic excursions and body weight and improve
      glycaemic control without increasing the risk of hypoglycaemia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in HbA1c
time frame: 6 months
description: Change in HbA1c from baseline to end of study (time 6 months)
measure: adverse events (including hypoglycaemic episodes)
time frame: 6 months
measure: changes in insulin dosage
time frame: 6 months
measure: changes in body weight
time frame: 6 months
measure: changes in BMI
time frame: 6 months
measure: changes in body composition
time frame: 6 months
description: DXA scan measuring bonemineral density
measure: changes in body composition
time frame: 6 months
description: DXA scan measuring lean mass
measure: changes in body composition
time frame: 6 months
description: DXA scan measuring fat mass
measure: changes in fasting plasma glucose
time frame: 6 months
measure: changes in post prandial plasma glucose
time frame: 6 months
measure: changes in fasting plasma levels of C-peptide
time frame: 6 months
measure: Quality of life self reported
time frame: 6 months
description: Quality of Life Questionaire
measure: Treatment satisfaction
time frame: 6 months
description: Diabetes treatment satisfactory questionnaire status version
measure: Treatment satisfaction
time frame: 6 months
description: Diabetes treatment satisfactory questionnaire change version
measure: dietary patterns
time frame: 6 months
description: Food frequency questionaire three times during the intervention
measure: HDL (High Density Lipoprotein)
time frame: 6 months
measure: LDL (Low Density Lipoprotein)
time frame: 6 months
measure: VLDL (Very Low Density Lipoprotein)
time frame: 6 months
measure: total cholesterol
time frame: 6 months
measure: triglycerides
time frame: 6 months
measure: proBNP (Pro-Brain Natriuretic Peptide)
time frame: 6 months
measure: hsCRP (High-Sensitivity C-Reactive Protein)
time frame: 6 months
arm group label: Intervention
arm group type: Experimental
description: Exenatide 10 mikrogram, thrice daily, subcutaneous injection prior to main meals, 6 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, thrice daily, subcutaneous injection prior to main meals, 6 months.
intervention type: Drug
intervention name: Exenatide
arm group label: Intervention
other name: Byetta
intervention type: Drug
intervention name: Placebos
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
country: Denmark
citation: Johansen NJ, Dejgaard TF, Lund A, Vilsboll T, Andersen HU, Knop FK. Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial. BMJ Open. 2018 Jun 27;8(6):e021861. doi: 10.1136/bmjopen-2018-021861.
PMID: 29950475
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Gentofte, Copenhagen
investigator full name: Filip Krag Knop
investigator title: Professor, MD, PhD
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Exenatide