<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/NCT01722240</url>
  </required_header>
  <id_info>
    <org_study_id>1966</org_study_id>
    <nct_id>NCT01722240</nct_id>
  </id_info>
  <brief_title>Liraglutide in Type 1 Diabetes</brief_title>
  <acronym>1966</acronym>
  <official_title>Liraglutide in Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University at Buffalo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University at Buffalo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The control of glucose homeostasis in subjects with type 1 diabetes is fragile since&#xD;
      exogenous insulin cannot compensate for changing requirements and is not precise either in&#xD;
      terms of the dose or the bio-availability of the insulin injected. Furthermore, in the near&#xD;
      total absence of insulin secretion, the physiological post prandial inhibition of glucagon&#xD;
      secretion by the α-cell is also probably deficient in all type 1 diabetics. Thus, there is a&#xD;
      need for therapies beyond insulin that can further improve glycemic control and reduce&#xD;
      fluctuations in glucose in these subjects. The investigators have recently shown that&#xD;
      Liraglutide, a glucagon like peptide (GLP)-1 analogue with duration of action of 24 hours,&#xD;
      when added to insulin in subjects with well controlled type 1 diabetes reduces mean and&#xD;
      standard deviation of blood glucose, HbA1c and insulin requirements. Since C-peptide&#xD;
      concentrations did not alter following Liraglutide, it is likely that the suppression of&#xD;
      glucagon may have contributed to this effect. The glucose lowering effects of GLP-1 agonists&#xD;
      are well established in subjects with type 2 diabetes, however, these have not been studied&#xD;
      prospectively in subjects with type 1 diabetes. The investigators have, therefore, designed&#xD;
      this study to investigate the central hypothesis that in patients with type 1 diabetes,&#xD;
      Liraglutide has a glucose lowering effect. A major secondary objective of this study is to&#xD;
      elucidate the mechanisms responsible for its glucose lowering effects and those involved in&#xD;
      reducing the insulin dose. The specific aims of this proposal are:&#xD;
&#xD;
      Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases HbA1c,&#xD;
      fasting, postprandial and the overall mean glucose concentrations while decreasing the dose&#xD;
      of insulin required.&#xD;
&#xD;
      Aim 1.1: To compare the HbA1c, mean fasting, glucose, mean weekly glucose, standard deviation&#xD;
      of weekly blood glucose concentrations as recorded by continuous glucose monitoring and the&#xD;
      dose of insulin required prior to and following 52 weeks of treatment with 1.8 mg of&#xD;
      liraglutide daily.&#xD;
&#xD;
      Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and&#xD;
      after 52 weeks of treatment with 1.8 mg of liraglutide daily.&#xD;
&#xD;
      Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases basal and&#xD;
      postprandial glucagon concentrations and increases basal and postprandial C-peptide&#xD;
      concentrations.&#xD;
&#xD;
      Aim 2.1: To compare the basal and postprandial glucagon and C-peptide concentrations&#xD;
      following a test meal before and after 52 weeks of treatment with 1.8 mg of liraglutide&#xD;
      daily.&#xD;
&#xD;
      Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric&#xD;
      emptying.&#xD;
&#xD;
      Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and&#xD;
      after treatment with 1.8 mg of daily subcutaneous liraglutide.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2019</completion_date>
  <primary_completion_date type="Actual">March 2019</primary_completion_date>
  <phase>Phase 3</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>HbA1c</measure>
    <time_frame>52 Weeks</time_frame>
    <description>The primary endpoint of the study is to detect a difference in HbA1c after 52 weeks of treatment with Liraglutide or placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean weekly glucose concentrations.</measure>
    <time_frame>52 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">96</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Liraglutide 1.8mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Daily Injection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily Injection</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liraglutide 1.8mg</intervention_name>
    <arm_group_label>Liraglutide 1.8mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII; also known as&#xD;
             insulin pump) or multiple (four or more) injections of insulin per day.&#xD;
&#xD;
          2. Regularly measuring blood sugars four times daily.&#xD;
&#xD;
          3. HbA1c of less than 8.5%.&#xD;
&#xD;
          4. Well versed with carbohydrate counting.&#xD;
&#xD;
          5. Age 18-75 years.&#xD;
&#xD;
          6. BMI 20-40 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Type 1 diabetes for less than 6 months;&#xD;
&#xD;
          2. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery&#xD;
             bypass, surgery or coronary angioplasty) in the previous four weeks;&#xD;
&#xD;
          3. Hepatic disease (transaminase &gt; 3 times normal) or cirrhosis;&#xD;
&#xD;
          4. Renal impairment (serum eGFR &lt; 30ml/min/1.73m2);&#xD;
&#xD;
          5. HIV or Hepatitis B or C positive status;&#xD;
&#xD;
          6. Participation in any other concurrent clinical trial;&#xD;
&#xD;
          7. Any other life-threatening, non-cardiac disease;&#xD;
&#xD;
          8. Use of an investigational agent or therapeutic regimen within 30 days of study.&#xD;
&#xD;
          9. history of pancreatitis&#xD;
&#xD;
         10. pregnancy&#xD;
&#xD;
         11. inability to give informed consent&#xD;
&#xD;
         12. history of gastroparesis&#xD;
&#xD;
         13. history of medullary thyroid carcinoma or MEN 2 syndrome.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paresh Dandona, MBBS, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaleida Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Diabetes-Endocrinology Center of WNY</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 2, 2012</study_first_submitted>
  <study_first_submitted_qc>November 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 6, 2012</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 3, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University at Buffalo</investigator_affiliation>
    <investigator_full_name>Paresh Dandona</investigator_full_name>
    <investigator_title>Director, Diabetes-Endocrinology Center of Western NY</investigator_title>
  </responsible_party>
  <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>Liraglutide</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>November 17, 2022</submitted>
    <returned>December 14, 2022</returned>
  </pending_results>
  <!-- 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/NCT01722240
org study id: 1966
nct id: NCT01722240
lead sponsor: 
collaborator: 
has dmc: Yes
The control of glucose homeostasis in subjects with type 1 diabetes is fragile since
      exogenous insulin cannot compensate for changing requirements and is not precise either in
      terms of the dose or the bio-availability of the insulin injected. Furthermore, in the near
      total absence of insulin secretion, the physiological post prandial inhibition of glucagon
      secretion by the α-cell is also probably deficient in all type 1 diabetics. Thus, there is a
      need for therapies beyond insulin that can further improve glycemic control and reduce
      fluctuations in glucose in these subjects. The investigators have recently shown that
      Liraglutide, a glucagon like peptide (GLP)-1 analogue with duration of action of 24 hours,
      when added to insulin in subjects with well controlled type 1 diabetes reduces mean and
      standard deviation of blood glucose, HbA1c and insulin requirements. Since C-peptide
      concentrations did not alter following Liraglutide, it is likely that the suppression of
      glucagon may have contributed to this effect. The glucose lowering effects of GLP-1 agonists
      are well established in subjects with type 2 diabetes, however, these have not been studied
      prospectively in subjects with type 1 diabetes. The investigators have, therefore, designed
      this study to investigate the central hypothesis that in patients with type 1 diabetes,
      Liraglutide has a glucose lowering effect. A major secondary objective of this study is to
      elucidate the mechanisms responsible for its glucose lowering effects and those involved in
      reducing the insulin dose. The specific aims of this proposal are:

      Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases HbA1c,
      fasting, postprandial and the overall mean glucose concentrations while decreasing the dose
      of insulin required.

      Aim 1.1: To compare the HbA1c, mean fasting, glucose, mean weekly glucose, standard deviation
      of weekly blood glucose concentrations as recorded by continuous glucose monitoring and the
      dose of insulin required prior to and following 52 weeks of treatment with 1.8 mg of
      liraglutide daily.

      Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and
      after 52 weeks of treatment with 1.8 mg of liraglutide daily.

      Hypothesis 2: Treatment with Liraglutide in patients with type 1 diabetes decreases basal and
      postprandial glucagon concentrations and increases basal and postprandial C-peptide
      concentrations.

      Aim 2.1: To compare the basal and postprandial glucagon and C-peptide concentrations
      following a test meal before and after 52 weeks of treatment with 1.8 mg of liraglutide
      daily.

      Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric
      emptying.

      Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and
      after treatment with 1.8 mg of daily subcutaneous liraglutide.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: HbA1c
time frame: 52 Weeks
description: The primary endpoint of the study is to detect a difference in HbA1c after 52 weeks of treatment with Liraglutide or placebo.
measure: Mean weekly glucose concentrations.
time frame: 52 Weeks
arm group label: Liraglutide 1.8mg
arm group type: Active Comparator
description: Daily Injection
arm group label: Placebo
arm group type: Placebo Comparator
description: Daily Injection
intervention type: Drug
intervention name: Liraglutide 1.8mg
arm group label: Liraglutide 1.8mg
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paresh Dandona, MBBS, PhD
role: Principal Investigator
affiliation: Kaleida Health
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University at Buffalo
investigator full name: Paresh Dandona
investigator title: Director, Diabetes-Endocrinology Center of Western NY
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Liraglutide
submitted: November 17, 2022
returned: December 14, 2022