<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/NCT02977442</url>
  </required_header>
  <id_info>
    <org_study_id>PBRC 2018-020</org_study_id>
    <nct_id>NCT02977442</nct_id>
  </id_info>
  <brief_title>Dynamics of Muscle Mitochondria in Type 2 Diabetes Exercise</brief_title>
  <acronym>DYNAMMO-T2DEX</acronym>
  <official_title>Dynamics of Muscle Mitochondria in Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pennington Biomedical Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pennington Biomedical Research Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells&#xD;
      for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes&#xD;
      occurs when the cells of the body become resistant to the effects of insulin, and this causes&#xD;
      high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the&#xD;
      heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed&#xD;
      at preventing and treating type 2 diabetes.&#xD;
&#xD;
      Mitochondria are cellular structures that are responsible for turning nutrients from food,&#xD;
      into the energy that our cells run on. As a result, mitochondria are known as &quot;the powerhouse&#xD;
      of the cell.&quot; Mitochondria are dynamic organelles that can move within a cell to the areas&#xD;
      where they are needed, and can fuse together to form large, string-like, tubular networks or&#xD;
      divide into small spherical structures. The name of this process is &quot;mitochondrial dynamics&quot;&#xD;
      and the process keeps the cells healthy. However, when more food is consumed compared to the&#xD;
      amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a&#xD;
      leak of partially metabolized nutrients that can interfere with the ability of insulin to&#xD;
      communicate within the cell. This may be a way for the cells to prevent further uptake of&#xD;
      nutrients until the current supply has been exhausted. However, long term overload of the&#xD;
      mitochondria may cause blood sugar levels to rise and lead to the development of type 2&#xD;
      diabetes.&#xD;
&#xD;
      This study will provide information about the relationship between mitochondrial dynamics,&#xD;
      insulin resistance and type 2 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The traditional view of mitochondria as isolated, spherical, energy producing organelles is&#xD;
      undergoing a revolutionary transformation. Emerging data show that mitochondria form a&#xD;
      dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery&#xD;
      of a number of proteins that regulate these activities has led to important advances in&#xD;
      understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a&#xD;
      protein that controls mitochondrial fission, is reduced following exercise in prediabetes,&#xD;
      and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed&#xD;
      research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin&#xD;
      resistance in type 2 diabetes. The experimental approach harnesses innovative molecular and&#xD;
      cellular tools, interfaced with physiologically significant human studies to obtain&#xD;
      meaningful data on insulin resistance, and has the potential to generate insights that will&#xD;
      lead to new diabetes therapies for future generations.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">September 2023</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effects of exercise on mitochondrial dynamics</measure>
    <time_frame>5 years</time_frame>
    <description>Dynamics will be assessed from quantitative measures of dynamin-related protein-1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effects of exercise on mitochondrial function</measure>
    <time_frame>5 years</time_frame>
    <description>Function will be assessed from oxygen consumption.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin sensitivity</measure>
    <time_frame>5 years</time_frame>
    <description>Insulin sensitivity will be assessed by euglycemic hyperinsulinemic clamp.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Insulin Resistance, Diabetes</condition>
  <arm_group>
    <arm_group_label>exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>12 week exercise program, 5 days/week, 60 min/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>standard of care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>12 week standard of care recommendations</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>exercise</intervention_name>
    <arm_group_label>exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 Diabetes&#xD;
&#xD;
          -  Body Mass Index (BMI) between 25 and 40 kg&#xD;
&#xD;
          -  HbA1C &lt; 8.5%&#xD;
&#xD;
          -  sedentary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pharmacotherapy for diabetes&#xD;
&#xD;
          -  smoking&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Kirwan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Pennington Biomedical Research Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pennington Biomedical Research Center</name>
      <address>
        <city>Baton Rouge</city>
        <state>Louisiana</state>
        <zip>70808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>November 28, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Pennington Biomedical Research Center</investigator_affiliation>
    <investigator_full_name>John Kirwan</investigator_full_name>
    <investigator_title>Executive Director</investigator_title>
  </responsible_party>
  <keyword>Mitochondrial Dynamics</keyword>
  <keyword>Insulin Resistance</keyword>
  <keyword>Exercise and Diabetes</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_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/NCT02977442
org study id: PBRC 2018-020
nct id: NCT02977442
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Insulin promotes the clearance of sugars from the blood into skeletal muscle and fat cells
      for use as energy; it also promotes storage of excess nutrients as fat. Type 2 diabetes
      occurs when the cells of the body become resistant to the effects of insulin, and this causes
      high blood sugar and contributes to a build-up of fat in muscle, pancreas, liver, and the
      heart. Understanding how insulin resistance occurs will pave the way for new therapies aimed
      at preventing and treating type 2 diabetes.

      Mitochondria are cellular structures that are responsible for turning nutrients from food,
      into the energy that our cells run on. As a result, mitochondria are known as "the powerhouse
      of the cell." Mitochondria are dynamic organelles that can move within a cell to the areas
      where they are needed, and can fuse together to form large, string-like, tubular networks or
      divide into small spherical structures. The name of this process is "mitochondrial dynamics"
      and the process keeps the cells healthy. However, when more food is consumed compared to the
      amount of energy burned, mitochondria may become overloaded and dysfunctional resulting in a
      leak of partially metabolized nutrients that can interfere with the ability of insulin to
      communicate within the cell. This may be a way for the cells to prevent further uptake of
      nutrients until the current supply has been exhausted. However, long term overload of the
      mitochondria may cause blood sugar levels to rise and lead to the development of type 2
      diabetes.

      This study will provide information about the relationship between mitochondrial dynamics,
      insulin resistance and type 2 diabetes.
The traditional view of mitochondria as isolated, spherical, energy producing organelles is
      undergoing a revolutionary transformation. Emerging data show that mitochondria form a
      dynamic networked reticulum that is regulated by cycles of fission and fusion. The discovery
      of a number of proteins that regulate these activities has led to important advances in
      understanding human disease. Data show that activation of dynamin related protein 1 (Drp1), a
      protein that controls mitochondrial fission, is reduced following exercise in prediabetes,
      and the decrease is linked to increased insulin sensitivity and fat oxidation. The proposed
      research will test the hypothesis that mitochondrial dynamics is a key mechanism of insulin
      resistance in type 2 diabetes. The experimental approach harnesses innovative molecular and
      cellular tools, interfaced with physiologically significant human studies to obtain
      meaningful data on insulin resistance, and has the potential to generate insights that will
      lead to new diabetes therapies for future generations.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Effects of exercise on mitochondrial dynamics
time frame: 5 years
description: Dynamics will be assessed from quantitative measures of dynamin-related protein-1.
measure: Effects of exercise on mitochondrial function
time frame: 5 years
description: Function will be assessed from oxygen consumption.
measure: Insulin sensitivity
time frame: 5 years
description: Insulin sensitivity will be assessed by euglycemic hyperinsulinemic clamp.
arm group label: exercise
arm group type: Experimental
description: 12 week exercise program, 5 days/week, 60 min/day
arm group label: standard of care
arm group type: No Intervention
description: 12 week standard of care recommendations
intervention type: Behavioral
intervention name: exercise
arm group label: exercise
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: John Kirwan, PhD
role: Principal Investigator
affiliation: Pennington Biomedical Research Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Pennington Biomedical Research Center
investigator full name: John Kirwan
investigator title: Executive Director
mesh term: Diabetes Mellitus
mesh term: Insulin Resistance
sharing ipd: No