<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/NCT01724502</url>
  </required_header>
  <id_info>
    <org_study_id>11-006065 Aim 4</org_study_id>
    <secondary_id>R01DK066483</secondary_id>
    <nct_id>NCT01724502</nct_id>
  </id_info>
  <brief_title>Mitochondrial Dysfunction in Diabetes</brief_title>
  <acronym>PGC-1</acronym>
  <official_title>PGC-1 and Mitochondrial Dysfunction in Diabetes, Aims 4 &amp; 5</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Mayo Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether insulin resistance is accompanied by&#xD;
      &quot;exercise resistance&quot;. Investigators will use mass spectrometry and proteomics analysis to&#xD;
      test the hypothesis is that a bout of exercise that increases mitochondrial protein abundance&#xD;
      in lean, healthy individuals is less effective in insulin resistant patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators' prior research has focused on defining the changes in expression of&#xD;
      nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal&#xD;
      muscle, with the goal of defining the molecular mechanisms underlying the connection between&#xD;
      mitochondrial dysfunction and insulin resistance in skeletal muscle.&#xD;
&#xD;
      Three groups of subjects will be studied: lean, healthy control subjects (n=12) obese&#xD;
      non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total of&#xD;
      36 subjects. Twenty subjects have completed the study at Arizona State University; the&#xD;
      remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.&#xD;
&#xD;
      Subjects will come to the Mayo Clinic 4 times. On Study Day 1 Subjects will be screened with&#xD;
      a medical history &amp; physical and a 75 g oral glucose tolerance test to determine if they are&#xD;
      eligible for the study. On Study Day 2, subjects will report to the clinic after an overnight&#xD;
      fast, undergo a euglycemic clamp (using deuterated glucose) to determine insulin sensitivity,&#xD;
      and in addition have a muscle biopsy (basal biopsy for comparison). On Study Day 3, subjects&#xD;
      will report to the clinic after an overnight fast, and undergo a Volume Oxygen Maximum (VO_2&#xD;
      max) determination. On Study Day 4, subjects will report to the clinic after an overnight&#xD;
      fast to perform an exercise bout with muscle biopsy 30 minutes after the end of exercise.&#xD;
      This will be followed by an overnight fast, and an additional muscle biopsy at 24 hours post&#xD;
      exercise.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Protein Concentration of Mitochondria</measure>
    <time_frame>Study Day 4 (30 min after exercise) and (24 hours after exercise)</time_frame>
    <description>Protein concentration will be determined from muscle biopsies by the method of Lowry. 75 micrograms of muscle lysate proteins will be separated on a 10% Sodium Dodecyl Sulfate Polyacrylamide Gel, and then visualized with Coomassie stain. The gel lane will be cut into cubes, digested with trypsin and cleaned, then protein abundance will be determined using spectral counting.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Diabetes</condition>
  <condition>Obese</condition>
  <arm_group>
    <arm_group_label>Obese Non-Diabetic Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects on this arm will undergo exercise and muscle biopsies.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Type 2 Diabetic Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects on this arm will undergo exercise and muscle biopsies.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Control Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All subjects on this arm will undergo exercise and muscle biopsies.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise and muscle biopsies</intervention_name>
    <description>Subjects will undergo a euglycemic clamp, VO_2 max determination, exercise periods and muscle biopsies.</description>
    <arm_group_label>Healthy Control Subjects</arm_group_label>
    <arm_group_label>Obese Non-Diabetic Subjects</arm_group_label>
    <arm_group_label>Type 2 Diabetic Subjects</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Subjects must be able to communicate meaningfully with the investigator and must be&#xD;
             legally competent to provide written informed consent.&#xD;
&#xD;
          2. Subjects may be of either sex with age as described in each protocol. Female subjects&#xD;
             must be non-lactating and will be eligible only if they have a negative pregnancy test&#xD;
             throughout the study period.&#xD;
&#xD;
          3. Subjects must range in age as described in each specific protocol.&#xD;
&#xD;
          4. Subjects must have the following laboratory values:&#xD;
&#xD;
               1. Hematocrit ≥ 35 vol%&#xD;
&#xD;
               2. Serum creatinine ≤ 1.6 mg/dl&#xD;
&#xD;
               3. Aspartate Aminotransferase (AST) (SGOT) &lt; 2 times upper limit of normal&#xD;
&#xD;
               4. Alanine Aminotransferase (ALT) (SGPT) &lt; 2 times upper limit of normal&#xD;
&#xD;
               5. Alkaline phosphatase &lt; 2 times upper limit of normal&#xD;
&#xD;
               6. Triglycerides &lt; 150 mg/dl.&#xD;
&#xD;
               7. Prothrombin Time (PT) 11.7 -14.3 seconds (during Intralipid/heparin infusion,PT&#xD;
                  will be determined to insure that it is &lt; 1.5-2.0 times the normal value.)&#xD;
&#xD;
               8. Partial thromboplastin time (PTT) 23.0-37.0 seconds.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Subjects must not be receiving any of the following medications: thiazide or&#xD;
             furosemide diuretics, beta-blockers, or other chronic medications with known adverse&#xD;
             effects on glucose tolerance levels unless the patient has been on a stable dose of&#xD;
             such agents for the past three months before entry into the study. Subjects may be&#xD;
             taking a stable dose of estrogens or other hormonal replacement therapy, if the&#xD;
             subject has been on these agents for the prior three months. Subjects taking systemic&#xD;
             glucocorticoids are excluded.&#xD;
&#xD;
          2. Subjects with a history of clinically significant heart disease (New York Heart&#xD;
             Classification greater than grade II; more than non-specific ST-T wave changes on the&#xD;
             EKG), peripheral vascular disease (history of claudication), or pulmonary disease&#xD;
             (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation)&#xD;
             will not be studied.&#xD;
&#xD;
          3. Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy,&#xD;
             recent retinal hemorrhage, uncontrolled hypertension, systolic BP&gt;180, diastolic&#xD;
             BP&gt;105, autonomic neuropathy, resting heart rate &gt;100, electrolyte abnormalities.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lawrence Mandarino, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic in Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://clinicaltrials.mayo.edu</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>May 2014</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>May 8, 2014</last_update_submitted>
  <last_update_submitted_qc>May 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 12, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Lawrence Mandarino</investigator_full_name>
    <investigator_title>Ph.D.</investigator_title>
  </responsible_party>
  <keyword>insulin resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_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/NCT01724502
org study id: 11-006065 Aim 4
secondary id: R01DK066483
nct id: NCT01724502
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to determine whether insulin resistance is accompanied by
      "exercise resistance". Investigators will use mass spectrometry and proteomics analysis to
      test the hypothesis is that a bout of exercise that increases mitochondrial protein abundance
      in lean, healthy individuals is less effective in insulin resistant patients.
The investigators' prior research has focused on defining the changes in expression of
      nuclear encoded mitochondrial genes that predict changes in insulin sensitivity in skeletal
      muscle, with the goal of defining the molecular mechanisms underlying the connection between
      mitochondrial dysfunction and insulin resistance in skeletal muscle.

      Three groups of subjects will be studied: lean, healthy control subjects (n=12) obese
      non-diabetic subjects (n=12) and patients with type 2 Diabetes Mellitus (n=12) for a total of
      36 subjects. Twenty subjects have completed the study at Arizona State University; the
      remaining 16 subjects will be accrued at the Mayo Clinic in Arizona.

      Subjects will come to the Mayo Clinic 4 times. On Study Day 1 Subjects will be screened with
      a medical history & physical and a 75 g oral glucose tolerance test to determine if they are
      eligible for the study. On Study Day 2, subjects will report to the clinic after an overnight
      fast, undergo a euglycemic clamp (using deuterated glucose) to determine insulin sensitivity,
      and in addition have a muscle biopsy (basal biopsy for comparison). On Study Day 3, subjects
      will report to the clinic after an overnight fast, and undergo a Volume Oxygen Maximum (VO_2
      max) determination. On Study Day 4, subjects will report to the clinic after an overnight
      fast to perform an exercise bout with muscle biopsy 30 minutes after the end of exercise.
      This will be followed by an overnight fast, and an additional muscle biopsy at 24 hours post
      exercise.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Protein Concentration of Mitochondria
time frame: Study Day 4 (30 min after exercise) and (24 hours after exercise)
description: Protein concentration will be determined from muscle biopsies by the method of Lowry. 75 micrograms of muscle lysate proteins will be separated on a 10% Sodium Dodecyl Sulfate Polyacrylamide Gel, and then visualized with Coomassie stain. The gel lane will be cut into cubes, digested with trypsin and cleaned, then protein abundance will be determined using spectral counting.
arm group label: Obese Non-Diabetic Subjects
arm group type: Experimental
description: All subjects on this arm will undergo exercise and muscle biopsies.
arm group label: Type 2 Diabetic Subjects
arm group type: Experimental
description: All subjects on this arm will undergo exercise and muscle biopsies.
arm group label: Healthy Control Subjects
arm group type: Experimental
description: All subjects on this arm will undergo exercise and muscle biopsies.
intervention type: Behavioral
intervention name: Exercise and muscle biopsies
description: Subjects will undergo a euglycemic clamp, VO_2 max determination, exercise periods and muscle biopsies.
arm group label: Healthy Control Subjects
arm group label: Obese Non-Diabetic Subjects
arm group label: Type 2 Diabetic Subjects
criteria: 
gender: All
minimum age: 21 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Lawrence Mandarino, Ph.D.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
country: United States
url: http://clinicaltrials.mayo.edu
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Lawrence Mandarino
investigator title: Ph.D.
mesh term: Diabetes Mellitus