<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/NCT02194595</url>
  </required_header>
  <id_info>
    <org_study_id>14-0128-A</org_study_id>
    <nct_id>NCT02194595</nct_id>
  </id_info>
  <brief_title>Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)</brief_title>
  <acronym>PREVAIL</acronym>
  <official_title>Preserving Beta-cell Function in Type 2 Diabetes With Exenatide and Insulin (PREVAIL)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mount Sinai Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mount Sinai Hospital, Canada</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive&#xD;
      deterioration in the function of the pancreatic beta-cells, which are the cells that produce&#xD;
      and secrete insulin (the hormone primarily responsible for the handling of glucose in the&#xD;
      body). The investigators propose a randomized controlled trial to determine whether combining&#xD;
      basal insulin with a new medication called exenatide is a therapeutic strategy that can&#xD;
      preserve beta-cell function early in the course of type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this open-label, parallel-arm randomized controlled trial, adults with T2DM of ≤7 years&#xD;
      duration on 0-2 anti-diabetic medications will be randomized to 8-weeks treatment with either&#xD;
      (i) basal insulin glargine, (ii) intensive insulin therapy consisting of glargine and&#xD;
      pre-meal insulin lispro, or (iii) glargine and the GLP-1 agonist exenatide (twice daily).&#xD;
      They will then go into a 12-week washout on lifestyle modification only. Beta-cell function&#xD;
      will be assessed by determining the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral&#xD;
      glucose tolerance test (OGTT) performed at baseline, 4-weeks, 8-weeks, and 20-weeks. The&#xD;
      primary outcome will be mean beta-cell function (ISSI-2) over the 8-week treatment period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">February 2022</completion_date>
  <primary_completion_date type="Actual">December 2021</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)</measure>
    <time_frame>8 weeks</time_frame>
    <description>ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index. The primary outcome comparison is between the glargine/exenatide and glargine only arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Baseline-adjusted beta-cell function at 20 weeks</measure>
    <time_frame>20 weeks</time_frame>
    <description>The secondary outcome of baseline-adjusted beta-cell function at 20 weeks will be measured with the Insulin Secretion-Sensitivity Index-2 (ISSI-2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline-adjusted glycemic control at 20 weeks</measure>
    <time_frame>20 weeks</time_frame>
    <description>The secondary outcome of baseline-adjusted glycemic control at 20 weeks will be assessed by A1c (glycated hemoglobin)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial function at 8 weeks</measure>
    <time_frame>8 weeks</time_frame>
    <description>Endothelial function will be assessed as the digital endothelial vasomotor function in response to reactive hyperemia using pulse amplitude tonometry, which will be measured by the pulse amplitude response to hyperemia (PAT ratio)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline-adjusted glycemic control at 8 weeks</measure>
    <time_frame>8 weeks</time_frame>
    <description>Baseline-adjusted glycemic control at 8 weeks will be measured by A1c</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Baseline-adjusted insulin sensitivity at 8 weeks</measure>
    <time_frame>8 weeks</time_frame>
    <description>Baseline-adjusted insulin sensitivity at 8 weeks will be measured by Matsuda index</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline-adjusted insulin sensitivity at 20 weeks</measure>
    <time_frame>20 weeks</time_frame>
    <description>Baseline-adjusted insulin sensitivity at 20 weeks will be measured by Matsuda index</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">105</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Basal insulin and exenatide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will undergo an 8-week course of treatment with exenatide and insulin glargine. Exenatide will be initiated at 5ug subcutaneous (sc) bid (before breakfast and before dinner) for the first 4 weeks, followed by 10ug bid for the next 4 weeks. Glargine sc injection at bedtime will be titrated to fasting glucose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Basal insulin only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm will undergo an 8-week course of treatment with glargine sc injection at bedtime, titrated to target fasting glucose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Basal Insulin and bolus insulin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this arm will undergo an 8-week course of multiple daily insulin injection therapy, consisting of titrated basal insulin glargine at bedtime and insulin lispro before each meal.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Basal insulin and exenatide</intervention_name>
    <arm_group_label>Basal insulin and exenatide</arm_group_label>
    <other_name>Basal insulin glargine</other_name>
    <other_name>Exenatide</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Basal insulin only</intervention_name>
    <arm_group_label>Basal insulin only</arm_group_label>
    <other_name>Basal insulin glargine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Basal insulin and bolus insulin</intervention_name>
    <arm_group_label>Basal Insulin and bolus insulin</arm_group_label>
    <other_name>Basal insulin glargine</other_name>
    <other_name>Pre-meal insulin lispro</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women between the ages of 30 and 80 years inclusive&#xD;
&#xD;
          2. T2DM diagnosed by a physician ≤7 years prior to enrolment&#xD;
&#xD;
          3. On 0-2 anti-diabetic medications, with no change in dose/regimen in the preceding 4&#xD;
             weeks&#xD;
&#xD;
          4. A1c at screening between 5.5% and 9.0% inclusive if on anti-diabetic medications, or&#xD;
             between 6.0% and 9.5% inclusive if on no oral anti-diabetic medication&#xD;
&#xD;
          5. BMI ≥ 23 kg/m2&#xD;
&#xD;
          6. Negative pregnancy test at recruitment for all women with childbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current anti-diabetic treatment with insulin or a glucagon-like peptide-1 (GLP-1)&#xD;
             agonist&#xD;
&#xD;
          2. Type 1 diabetes or secondary forms of diabetes&#xD;
&#xD;
          3. History of hypoglycemia unawareness or severe hypoglycemia requiring assistance&#xD;
&#xD;
          4. Hypersensitivity to insulin, exenatide, or the formulations of these products&#xD;
&#xD;
          5. Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR)&lt;30&#xD;
             ml/min by Modification of Diet in Renal Disease (MDRD) formula&#xD;
&#xD;
          6. History of pancreatitis&#xD;
&#xD;
          7. Family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial&#xD;
             medullary thyroid carcinoma (MTC)&#xD;
&#xD;
          8. Personal history of non-familial medullary thyroid carcinoma (MTC)&#xD;
&#xD;
          9. Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy&#xD;
             within the previous 5 years (with the exception of basal cell skin cancer)&#xD;
&#xD;
         10. Unwillingness to perform capillary glucose monitoring at least 4 times a day during&#xD;
             treatment&#xD;
&#xD;
         11. Pregnancy or unwillingness to use reliable contraception. Women should not be planning&#xD;
             pregnancy for the duration of the study or the first 3 months after the study.&#xD;
             Reliable contraception includes birth control pill, intra-uterine device, abstinence,&#xD;
             tubal ligation, partner vasectomy, or condoms with spermicide.&#xD;
&#xD;
         12. Any factor likely to limit adherence to the protocol, in the opinion of investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ravi Retnakaran, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MOUNT SINAI HOSPITAL</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G1X5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 18, 2014</study_first_posted>
  <last_update_submitted>April 7, 2022</last_update_submitted>
  <last_update_submitted_qc>April 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>type 2 diabetes</keyword>
  <keyword>beta-cell function</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 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Insulin Glargine</mesh_term>
    <mesh_term>Exenatide</mesh_term>
    <mesh_term>Insulin Lispro</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/NCT02194595
org study id: 14-0128-A
nct id: NCT02194595
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by progressive
      deterioration in the function of the pancreatic beta-cells, which are the cells that produce
      and secrete insulin (the hormone primarily responsible for the handling of glucose in the
      body). The investigators propose a randomized controlled trial to determine whether combining
      basal insulin with a new medication called exenatide is a therapeutic strategy that can
      preserve beta-cell function early in the course of type 2 diabetes.
In this open-label, parallel-arm randomized controlled trial, adults with T2DM of ≤7 years
      duration on 0-2 anti-diabetic medications will be randomized to 8-weeks treatment with either
      (i) basal insulin glargine, (ii) intensive insulin therapy consisting of glargine and
      pre-meal insulin lispro, or (iii) glargine and the GLP-1 agonist exenatide (twice daily).
      They will then go into a 12-week washout on lifestyle modification only. Beta-cell function
      will be assessed by determining the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral
      glucose tolerance test (OGTT) performed at baseline, 4-weeks, 8-weeks, and 20-weeks. The
      primary outcome will be mean beta-cell function (ISSI-2) over the 8-week treatment period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean beta-cell function over the 8-week treatment period, measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
time frame: 8 weeks
description: ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index. The primary outcome comparison is between the glargine/exenatide and glargine only arms.
measure: Baseline-adjusted beta-cell function at 20 weeks
time frame: 20 weeks
description: The secondary outcome of baseline-adjusted beta-cell function at 20 weeks will be measured with the Insulin Secretion-Sensitivity Index-2 (ISSI-2)
measure: Baseline-adjusted glycemic control at 20 weeks
time frame: 20 weeks
description: The secondary outcome of baseline-adjusted glycemic control at 20 weeks will be assessed by A1c (glycated hemoglobin)
measure: Endothelial function at 8 weeks
time frame: 8 weeks
description: Endothelial function will be assessed as the digital endothelial vasomotor function in response to reactive hyperemia using pulse amplitude tonometry, which will be measured by the pulse amplitude response to hyperemia (PAT ratio)
measure: Baseline-adjusted glycemic control at 8 weeks
time frame: 8 weeks
description: Baseline-adjusted glycemic control at 8 weeks will be measured by A1c
measure: Baseline-adjusted insulin sensitivity at 8 weeks
time frame: 8 weeks
description: Baseline-adjusted insulin sensitivity at 8 weeks will be measured by Matsuda index
measure: Baseline-adjusted insulin sensitivity at 20 weeks
time frame: 20 weeks
description: Baseline-adjusted insulin sensitivity at 20 weeks will be measured by Matsuda index
arm group label: Basal insulin and exenatide
arm group type: Experimental
description: Participants in this arm will undergo an 8-week course of treatment with exenatide and insulin glargine. Exenatide will be initiated at 5ug subcutaneous (sc) bid (before breakfast and before dinner) for the first 4 weeks, followed by 10ug bid for the next 4 weeks. Glargine sc injection at bedtime will be titrated to fasting glucose.
arm group label: Basal insulin only
arm group type: Active Comparator
description: Participants in this arm will undergo an 8-week course of treatment with glargine sc injection at bedtime, titrated to target fasting glucose.
arm group label: Basal Insulin and bolus insulin
arm group type: Active Comparator
description: Participants in this arm will undergo an 8-week course of multiple daily insulin injection therapy, consisting of titrated basal insulin glargine at bedtime and insulin lispro before each meal.
intervention type: Drug
intervention name: Basal insulin and exenatide
arm group label: Basal insulin and exenatide
other name: Basal insulin glargine
other name: Exenatide
intervention type: Drug
intervention name: Basal insulin only
arm group label: Basal insulin only
other name: Basal insulin glargine
intervention type: Drug
intervention name: Basal insulin and bolus insulin
arm group label: Basal Insulin and bolus insulin
other name: Basal insulin glargine
other name: Pre-meal insulin lispro
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ravi Retnakaran, MD
role: Principal Investigator
affiliation: MOUNT SINAI HOSPITAL
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Insulin Glargine
mesh term: Exenatide
mesh term: Insulin Lispro