<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/NCT04409795</url>
  </required_header>
  <id_info>
    <org_study_id>2019-76</org_study_id>
    <nct_id>NCT04409795</nct_id>
  </id_info>
  <brief_title>Oral Hypoglycemic Therapy for Monogenic Variant Carriers of the Joslin Medalist Study</brief_title>
  <official_title>A Pilot Trial of Adding Oral Hypoglycemic Therapy to Insulin Treatment in Monogenic Variant Carriers of the Joslin 50-Year Medalist Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joslin Diabetes Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Joslin Diabetes Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents&#xD;
      (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year&#xD;
      Medalist Study (&quot;Medalists&quot;), who are characterized by ≥50 years of insulin-dependent&#xD;
      diabetes. Our primary objective is to evaluate whether the presence of human leukocyte&#xD;
      antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of&#xD;
      OHA in these subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">August 26, 2021</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Glycated hemoglobin (HbA1c)</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in HbA1c (%) between the two study groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Daily insulin dose</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in daily insulin dose (units/kg body weight) between the two study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body mass index (BMI)</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in BMI between the two study groups. Weight and height will be combined to report BMI in kg/m^2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-peptide</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in C-peptide (ng/mL) between the two study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in total cholesterol (mg/dL) between the two study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low density lipoprotein (LDL)-cholesterol</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in LDL-cholesterol (mg/dL) between the two study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High density lipoprotein (HDL)-cholesterol</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in HDL-cholesterol (mg/dL) between the two study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglycerides</measure>
    <time_frame>3 months and 6 months</time_frame>
    <description>Change in triglycerides (mg/dL) between the two study groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of C-peptide</measure>
    <time_frame>6 months</time_frame>
    <description>Change in AUC of C-peptide between the two study groups, as measured by the hyperglycemic/arginine clamp, at the end of the study</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">21</enrollment>
  <condition>Type 1 Diabetes</condition>
  <condition>Monogenic Diabetes</condition>
  <arm_group>
    <arm_group_label>HLA+ Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score&gt;0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HLA- Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score&gt;0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin Extended Release Oral Tablet</intervention_name>
    <description>Initial oral hypoglycemic agent added to existing insulin treatment</description>
    <arm_group_label>HLA+ Group</arm_group_label>
    <arm_group_label>HLA- Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin</intervention_name>
    <description>Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)</description>
    <arm_group_label>HLA+ Group</arm_group_label>
    <arm_group_label>HLA- Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Existing participants in the Joslin 50-Year Medalist Study&#xD;
&#xD;
          -  Residing in the United States&#xD;
&#xD;
          -  Capable of giving informed consent&#xD;
&#xD;
          -  Known detectable C-peptide &gt;0.05 ng/mL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known diagnosis of cancer or active inflammatory disease such as rheumatoid arthritis,&#xD;
             lupus, and inflammatory bowel disease&#xD;
&#xD;
          -  Recent history of myocardial infarction, angioplasty, bypass surgery, heart failure,&#xD;
             angina, stroke, or uncontrolled hypertension&gt;160/100 during the past 3 months&#xD;
&#xD;
          -  Known diagnosis of cognitive dysfunction, dementia or Alzheimer's disease&#xD;
&#xD;
          -  Pre-existing liver disease or liver function tests (AST or ALT)&gt;3x the upper limit of&#xD;
             normal&#xD;
&#xD;
          -  Pre-existing kidney disease (Chronic Kidney Disease Stage IV and below, or estimated&#xD;
             glomerular filtration rate&lt;45 mL/min/1.73 m2)&#xD;
&#xD;
          -  Active use of immunosuppressants&#xD;
&#xD;
          -  Recipients of prior islet cell or pancreas transplantation&#xD;
&#xD;
          -  Inability to travel due to frailty or health reasons&#xD;
&#xD;
          -  Donated blood within the previous two (2) months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>George L. King, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Joslin Diabetes Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Joslin Diabetes Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 14, 2019</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>February 22, 2023</last_update_submitted>
  <last_update_submitted_qc>February 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Sitagliptin Phosphate</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/NCT04409795
org study id: 2019-76
nct id: NCT04409795
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate the efficacy of adding oral hypoglycemic agents
      (OHA) to existing insulin treatment in monogenic variant carriers of the Joslin 50-Year
      Medalist Study ("Medalists"), who are characterized by ≥50 years of insulin-dependent
      diabetes. Our primary objective is to evaluate whether the presence of human leukocyte
      antigen (HLA) high-risk alleles for diabetes (DR3 and/or DR4) can affect the effectiveness of
      OHA in these subjects.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Glycated hemoglobin (HbA1c)
time frame: 3 months and 6 months
description: Change in HbA1c (%) between the two study groups
measure: Daily insulin dose
time frame: 3 months and 6 months
description: Change in daily insulin dose (units/kg body weight) between the two study groups
measure: Body mass index (BMI)
time frame: 3 months and 6 months
description: Change in BMI between the two study groups. Weight and height will be combined to report BMI in kg/m^2.
measure: C-peptide
time frame: 3 months and 6 months
description: Change in C-peptide (ng/mL) between the two study groups
measure: Total cholesterol
time frame: 3 months and 6 months
description: Change in total cholesterol (mg/dL) between the two study groups
measure: Low density lipoprotein (LDL)-cholesterol
time frame: 3 months and 6 months
description: Change in LDL-cholesterol (mg/dL) between the two study groups
measure: High density lipoprotein (HDL)-cholesterol
time frame: 3 months and 6 months
description: Change in HDL-cholesterol (mg/dL) between the two study groups
measure: Triglycerides
time frame: 3 months and 6 months
description: Change in triglycerides (mg/dL) between the two study groups
measure: Area under the plasma concentration versus time curve (AUC) of C-peptide
time frame: 6 months
description: Change in AUC of C-peptide between the two study groups, as measured by the hyperglycemic/arginine clamp, at the end of the study
arm group label: HLA+ Group
arm group type: Other
description: Participants who are high-risk HLA-DR3 and/or DR4 (+); monogenic variant (+) with rare exome variant ensemble learner (REVEL) score>0.75; and both glutamic acid decarboxylase (GAD65) and islet antigen (IA2) autoantibody (-)
arm group label: HLA- Group
arm group type: Other
description: Participants who are high-risk HLA-DR3 and DR4 (-); with known or yet unknown monogenic variants with REVEL score>0.75; and either GAD65 and IA2 autoantibody (-), or autoantibody (+) with titers close to the cutoff
intervention type: Drug
intervention name: Metformin Extended Release Oral Tablet
description: Initial oral hypoglycemic agent added to existing insulin treatment
arm group label: HLA+ Group
arm group label: HLA- Group
intervention type: Drug
intervention name: Sitagliptin
description: Secondary oral hypoglycemic agent added to existing insulin treatment (for those who are intolerant to or unable to achieve glycemic targets with metformin)
arm group label: HLA+ Group
arm group label: HLA- Group
criteria: 
gender: All
minimum age: N/A
maximum age: 85 Years
healthy volunteers: No
last name: George L. King, MD
role: Principal Investigator
affiliation: Joslin Diabetes Center
facility: 
country: United States
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Metformin
mesh term: Sitagliptin Phosphate