<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/NCT02192424</url>
  </required_header>
  <id_info>
    <org_study_id>12-0263-A Main</org_study_id>
    <nct_id>NCT02192424</nct_id>
  </id_info>
  <brief_title>Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes (RESET-IT Main Trial)</brief_title>
  <acronym>RESET-IT</acronym>
  <official_title>A Randomized Controlled Trial to Evaluate Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes: REmission Studies Evaluating Type 2 DM - Intermittent Insulin Therapy (RESET-IT)</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>
  </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&#xD;
      intermittent intensive insulin therapy is an effective therapeutic strategy that can preserve&#xD;
      pancreatic beta-cell function and maintain glycemic control early in the course of type 2&#xD;
      diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, eligible patients with type 2 diabetes will be randomized to either&#xD;
      intermittent insulin therapy or not, on a background of metformin, after first undergoing a&#xD;
      short course of intensive insulin therapy. The hypothesis under study is whether intermittent&#xD;
      insulin therapy can preserve beta-cell function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">September 2020</completion_date>
  <primary_completion_date type="Actual">August 2020</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).</measure>
    <time_frame>2 years</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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Baseline-adjusted glycemic control at 2-years.</measure>
    <time_frame>2 years</time_frame>
    <description>The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Achievement of target glycemic control</measure>
    <time_frame>2 years</time_frame>
    <description>Achievement of target glycemic control will be assessed by the proportion of participants with A1c &lt;7.0%</description>
  </other_outcome>
  <other_outcome>
    <measure>achievement of glucose tolerance in the non-diabetic range</measure>
    <time_frame>2 years</time_frame>
    <description>The proportion of participants with glucose tolerance in the non-diabetic range will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.</description>
  </other_outcome>
  <other_outcome>
    <measure>achievement of normal glucose tolerance</measure>
    <time_frame>2 years</time_frame>
    <description>The proportion of participants with normal glucose tolerance will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.</description>
  </other_outcome>
  <other_outcome>
    <measure>insulin sensitivity</measure>
    <time_frame>2 years</time_frame>
    <description>Insulin sensitivity will be measured by Matsuda index, a clamp-validated measure of whole-body insulin sensitivity that can be obtained from the oral glucose tolerance test</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">109</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Metformin alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy. Metformin will be initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin + Intermittent Insulin Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy, initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months). Participants will stop their metformin for 2 weeks every 3 months, during which time they will receive intermittent intensive insulin therapy for 2 weeks. The 2-week course of insulin therapy will be repeated at 3-, 6-, 9-, 12-, 15-,18- and 21-months, with final outcome measurement performed at 24-months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin alone</intervention_name>
    <arm_group_label>Metformin alone</arm_group_label>
    <other_name>metformin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin + Intermittent Insulin Therapy</intervention_name>
    <arm_group_label>Metformin + Intermittent Insulin Therapy</arm_group_label>
    <other_name>metformin,</other_name>
    <other_name>basal insulin glargine and 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 &lt;/= 5 years prior to enrolment&#xD;
&#xD;
          3. Negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies&#xD;
&#xD;
          4. On either no anti-diabetic medication or on metformin monotherapy, with no change in&#xD;
             dose/regimen within 4 weeks prior to enrolment&#xD;
&#xD;
          5. A1c at screening between 5.5% and 9.0% inclusive if on metformin, or between 6.0% and&#xD;
             9.5% inclusive if on no oral anti-diabetic medication&#xD;
&#xD;
          6. BMI &gt;/= 23 kg/m2&#xD;
&#xD;
          7. Negative pregnancy test at recruitment for all women with childbearing potential&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione,&#xD;
             alpha-glucosidase inhibitor, glucagon-like peptide-1 (GLP-1) agonist or dipeptidyl&#xD;
             peptidase-4 inhibitor&#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. Any major illness with a life expectancy of &lt;5 years&#xD;
&#xD;
          5. Hypersensitivity to insulin, metformin or the formulations of these products&#xD;
&#xD;
          6. Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) &lt;50&#xD;
             ml/min&#xD;
&#xD;
          7. Hepatic disease considered to be clinically significant (includes jaundice, chronic&#xD;
             hepatitis, previous liver transplant) or transaminases &gt;2.5 X upper limit of normal&#xD;
&#xD;
          8. History of congestive heart failure&#xD;
&#xD;
          9. Excessive alcohol consumption, defined as &gt;14 alcoholic drinks per week for males and&#xD;
             &gt;9 alcoholic drinks per week for females&#xD;
&#xD;
         10. Unwillingness to administer insulin therapy or perform capillary blood glucose&#xD;
             monitoring at least 4 times per day while receiving IIT&#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. Non-adherence to the induction phase or any factor likely to limit adherence to the&#xD;
             study protocol, in the opinion of the 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>October 2020</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>October 26, 2020</last_update_submitted>
  <last_update_submitted_qc>October 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>beta-cell function,</keyword>
  <keyword>type 2 diabetes,</keyword>
  <keyword>intermittent 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>Metformin</mesh_term>
    <mesh_term>Insulin Glargine</mesh_term>
    <mesh_term>Insulin Lispro</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02192424
org study id: 12-0263-A Main
nct id: NCT02192424
lead sponsor: 
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
      intermittent intensive insulin therapy is an effective therapeutic strategy that can preserve
      pancreatic beta-cell function and maintain glycemic control early in the course of type 2
      diabetes.
In this study, eligible patients with type 2 diabetes will be randomized to either
      intermittent insulin therapy or not, on a background of metformin, after first undergoing a
      short course of intensive insulin therapy. The hypothesis under study is whether intermittent
      insulin therapy can preserve beta-cell function.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).
time frame: 2 years
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.
measure: Baseline-adjusted glycemic control at 2-years.
time frame: 2 years
description: The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)
measure: Achievement of target glycemic control
time frame: 2 years
description: Achievement of target glycemic control will be assessed by the proportion of participants with A1c <7.0%
measure: achievement of glucose tolerance in the non-diabetic range
time frame: 2 years
description: The proportion of participants with glucose tolerance in the non-diabetic range will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.
measure: achievement of normal glucose tolerance
time frame: 2 years
description: The proportion of participants with normal glucose tolerance will be determined on oral glucose tolerance test (OGTT) and defined based on current Canadian Diabetes Association classifications for glucose tolerance status on OGTT.
measure: insulin sensitivity
time frame: 2 years
description: Insulin sensitivity will be measured by Matsuda index, a clamp-validated measure of whole-body insulin sensitivity that can be obtained from the oral glucose tolerance test
arm group label: Metformin alone
arm group type: Active Comparator
description: After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy. Metformin will be initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months).
arm group label: Metformin + Intermittent Insulin Therapy
arm group type: Experimental
description: After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy, initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months). Participants will stop their metformin for 2 weeks every 3 months, during which time they will receive intermittent intensive insulin therapy for 2 weeks. The 2-week course of insulin therapy will be repeated at 3-, 6-, 9-, 12-, 15-,18- and 21-months, with final outcome measurement performed at 24-months.
intervention type: Drug
intervention name: Metformin alone
arm group label: Metformin alone
other name: metformin
intervention type: Drug
intervention name: Metformin + Intermittent Insulin Therapy
arm group label: Metformin + Intermittent Insulin Therapy
other name: metformin,
other name: basal insulin glargine and 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: Metformin
mesh term: Insulin Glargine
mesh term: Insulin Lispro
sharing ipd: No