<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/NCT02218619</url>
  </required_header>
  <id_info>
    <org_study_id>AAAN2402</org_study_id>
    <nct_id>NCT02218619</nct_id>
  </id_info>
  <brief_title>Tauroursodeoxycholic Acid (TUDCA) in New-Onset Type 1 Diabetes</brief_title>
  <official_title>Clinical Investigation of Efficacy of Tauroursodeoxycholic Acid (TUDCA) to Enhance Pancreatic Beta Cell Survival In Type 1 Diabetes by Reducing Endoplasmic Reticulum Stress</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Robin Goland, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Juvenile Diabetes Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Clinically, the ability to slow or prevent beta cell demise can prevent or improve the course&#xD;
      of type 1 diabetes. The immune-mediated destruction of beta cells that is an apparent major&#xD;
      pathological basis for the disease, has led to efforts to prevent or suppress this immune&#xD;
      assault. Here we propose to buttress the beta cell's capacity to withstand this assault by&#xD;
      improving the function of the endoplasmic reticulum stress resolving mechanisms within these&#xD;
      cells. The ability to do so could have a major impact on preventive and therapeutic&#xD;
      strategies for type 1 diabetes (and possibly other types of diabetes). The type of&#xD;
      endoplasmic reticulum stress relieving agent (TUDCA) proposed here could ultimately be&#xD;
      applied on an anticipatory basis to individuals at high risk for type 1 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Reducing endoplasmic reticulum stress will promote beta cell survival in new-onset type 1&#xD;
      diabetes.&#xD;
&#xD;
      The primary aim is to test the clinical efficacy of an already approved agent, TUDCA,&#xD;
      re-purposed to reduce endoplasmic reticulum stress and improve beta cell survival in patients&#xD;
      with new onset type 1 diabetes. The primary endpoint of this proposed double-blinded&#xD;
      randomized placebo-controlled pilot study is c-peptide measured after mixed meal stimulation&#xD;
      test at randomization and then at 6 and 12 months of treatment with TUDCA compared to&#xD;
      treatment with placebo and at 6 months following treatment.&#xD;
&#xD;
      TUDCA is an oral medication with an excellent safety profile that is approved for use in&#xD;
      Europe for gall stones and liver disease. The drug and similar compounds has been used in&#xD;
      children, as young as newborns, and in adults. TUDCA's ability to lower endoplasmic reticulum&#xD;
      stress has only recently been recognized and will be applied to new-onset type 1 diabetes in&#xD;
      this proposal. If this pilot trial is successful, future studies could include broadening the&#xD;
      recipients to antibody-positive pre-type 1 diabetes patients and/or combining TUDCA with&#xD;
      other agents shown to have a beneficial effect on insulin secretion in new-onset type 1&#xD;
      diabetes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2015</start_date>
  <completion_date type="Anticipated">October 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">October 1, 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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>C-peptide measurement as reflection of insulin secretion</measure>
    <time_frame>18 months</time_frame>
    <description>The primary endpoint will be the area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at screening, and during the 12 months of drug treatment at 6 and12 months and at 6 months after drug or placebo is stopped.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Endoplasmic reticulum stress</measure>
    <time_frame>1 week</time_frame>
    <description>It is believed that the autoimmune assault of new onset type 1 diabetes leads to stress to the part of the beta cell that folds proteins; referred to as endoplasmic reticulum stress. When endoplasmic reticulum stress increases, changes in protein levels in beta cells occur. We will measure markers of endoplasmic reticulum stress in beta cells taken from skin biopsies taken from subjects before treatment with TUDCA or placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>liver function tests</measure>
    <time_frame>18 months</time_frame>
    <description>We will measure liver function tests at 6 and 12 months and at 6 months after drug or placebo is stopped to ensure that no abnormalities of liver function occur with the drug.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Taurourodeoxycholic Acid (TUDCA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TUDCA 1750 mg/day x 12 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar pill (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo at same dose, frequency, and duration as experimental treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tauroursodeoxycholic Acid (TUDCA)</intervention_name>
    <description>TUDCA at 1750 mg/day x 12 months</description>
    <arm_group_label>Taurourodeoxycholic Acid (TUDCA)</arm_group_label>
    <other_name>TUDCA</other_name>
    <other_name>Taurolite</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugar Pill (placebo)</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Sugar pill (placebo)</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes according to American Diabetes Association criteria&#xD;
&#xD;
          -  Diagnosis of type 1 diabetes within 100 days of randomization&#xD;
&#xD;
          -  One positive diabetes-related autoantibody&#xD;
&#xD;
          -  Ages 18-45 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Drugs known to affect glucose other than insulin&#xD;
&#xD;
          -  Stimulated C-peptide levels &lt; 0.2 pmol/ml measured during a mixed meal tolerance test&#xD;
             conducted at least 21 days from diagnosis of diabetes and within one month (37 days)&#xD;
             of randomization to either TUDCA or placebo.&#xD;
&#xD;
          -  Women during pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robin Goland, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rudolph Leibel, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Naomi Berrie Diabetes Center, Columbia University, 1150 St. Nicholas Ave.</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>December 3, 2018</last_update_submitted>
  <last_update_submitted_qc>December 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 4, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Robin Goland, MD</investigator_full_name>
    <investigator_title>J. Merrill Eastman Professor of Clinical Diabetes, Co-Director, Berrie Center</investigator_title>
  </responsible_party>
  <keyword>type 1 diabetes (T1D)</keyword>
  <keyword>endoplasmic reticulum (ER) stress</keyword>
  <keyword>induced pluripotential stem (iPS) cells</keyword>
  <keyword>Tauroursodeoxycholic Acid (TUDCA)</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>Ursodoxicoltaurine</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>April 12, 2022</submitted>
    <returned>May 6, 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/NCT02218619
org study id: AAAN2402
nct id: NCT02218619
lead sponsor: 
collaborator: 
has dmc: Yes
Clinically, the ability to slow or prevent beta cell demise can prevent or improve the course
      of type 1 diabetes. The immune-mediated destruction of beta cells that is an apparent major
      pathological basis for the disease, has led to efforts to prevent or suppress this immune
      assault. Here we propose to buttress the beta cell's capacity to withstand this assault by
      improving the function of the endoplasmic reticulum stress resolving mechanisms within these
      cells. The ability to do so could have a major impact on preventive and therapeutic
      strategies for type 1 diabetes (and possibly other types of diabetes). The type of
      endoplasmic reticulum stress relieving agent (TUDCA) proposed here could ultimately be
      applied on an anticipatory basis to individuals at high risk for type 1 diabetes.
Reducing endoplasmic reticulum stress will promote beta cell survival in new-onset type 1
      diabetes.

      The primary aim is to test the clinical efficacy of an already approved agent, TUDCA,
      re-purposed to reduce endoplasmic reticulum stress and improve beta cell survival in patients
      with new onset type 1 diabetes. The primary endpoint of this proposed double-blinded
      randomized placebo-controlled pilot study is c-peptide measured after mixed meal stimulation
      test at randomization and then at 6 and 12 months of treatment with TUDCA compared to
      treatment with placebo and at 6 months following treatment.

      TUDCA is an oral medication with an excellent safety profile that is approved for use in
      Europe for gall stones and liver disease. The drug and similar compounds has been used in
      children, as young as newborns, and in adults. TUDCA's ability to lower endoplasmic reticulum
      stress has only recently been recognized and will be applied to new-onset type 1 diabetes in
      this proposal. If this pilot trial is successful, future studies could include broadening the
      recipients to antibody-positive pre-type 1 diabetes patients and/or combining TUDCA with
      other agents shown to have a beneficial effect on insulin secretion in new-onset type 1
      diabetes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: C-peptide measurement as reflection of insulin secretion
time frame: 18 months
description: The primary endpoint will be the area under the stimulated C-peptide curve over the first 2 hours of a 4- hour mixed meal tolerance test conducted at screening, and during the 12 months of drug treatment at 6 and12 months and at 6 months after drug or placebo is stopped.
measure: Endoplasmic reticulum stress
time frame: 1 week
description: It is believed that the autoimmune assault of new onset type 1 diabetes leads to stress to the part of the beta cell that folds proteins; referred to as endoplasmic reticulum stress. When endoplasmic reticulum stress increases, changes in protein levels in beta cells occur. We will measure markers of endoplasmic reticulum stress in beta cells taken from skin biopsies taken from subjects before treatment with TUDCA or placebo.
measure: liver function tests
time frame: 18 months
description: We will measure liver function tests at 6 and 12 months and at 6 months after drug or placebo is stopped to ensure that no abnormalities of liver function occur with the drug.
arm group label: Taurourodeoxycholic Acid (TUDCA)
arm group type: Experimental
description: TUDCA 1750 mg/day x 12 months
arm group label: Sugar pill (placebo)
arm group type: Placebo Comparator
description: Placebo at same dose, frequency, and duration as experimental treatment
intervention type: Drug
intervention name: Tauroursodeoxycholic Acid (TUDCA)
description: TUDCA at 1750 mg/day x 12 months
arm group label: Taurourodeoxycholic Acid (TUDCA)
other name: TUDCA
other name: Taurolite
intervention type: Drug
intervention name: Sugar Pill (placebo)
description: Placebo
arm group label: Sugar pill (placebo)
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Robin Goland, MD
role: Principal Investigator
affiliation: Columbia University
last name: Rudolph Leibel, MD
role: Principal Investigator
affiliation: Columbia University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Columbia University
investigator full name: Robin Goland, MD
investigator title: J. Merrill Eastman Professor of Clinical Diabetes, Co-Director, Berrie Center
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
mesh term: Ursodoxicoltaurine
submitted: April 12, 2022
returned: May 6, 2022