<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/NCT01724515</url>
  </required_header>
  <id_info>
    <org_study_id>11-006065 Aim 5</org_study_id>
    <secondary_id>R01DK066483</secondary_id>
    <nct_id>NCT01724515</nct_id>
  </id_info>
  <brief_title>PGC-1 and Mitochondrial Dysfunction in Diabetes</brief_title>
  <official_title>PGC-1 and Mitochondrial Dysfunction in Diabetes</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 determine if you have too much fat in your body that it will&#xD;
      decrease the conversion of food energy into energy that your body can use.&#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;
      The purpose of this study is to determine whether experimental lipid oversupply decreases&#xD;
      mitochondrial respiratory function. We will use mitochondrial respiration studies in vitro&#xD;
      and mass spectrometry and proteomics analysis to test the hypothesis that experimental lipid&#xD;
      oversupply:&#xD;
&#xD;
        1. Decreases mitochondrial respiration in response to lipid fuels.&#xD;
&#xD;
        2. Reduces abundance of mitochondrial proteins.&#xD;
&#xD;
        3. Alters phosphorylation of proteins in the electron transport chain.&#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 2 times. On study Day 1 subjects will be screened with&#xD;
      a medical history and physical exam, and a 75 g oral glucose tolerance test, measure body fat&#xD;
      percentage, and an electrocardiogram (EKG). On Study Day 2, subjects will report to the&#xD;
      clinic after an overnight fast. Female subjects will take a urine pregnancy test. A muscle&#xD;
      biopsy will be performed to take a small sample from one thigh. A lipid infusion will be&#xD;
      performed for 5 hours (60 ml/hr), with blood samples taken at 8 intervals during the&#xD;
      infusion. At the end of the 5 hour period, a second muscle biopsy will be taken from the&#xD;
      other thigh. The fat infusion will stop, subjects will be given lunch and allowed to leave&#xD;
      the clinic.&#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>Mitochondrial Respiration</measure>
    <time_frame>Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation</time_frame>
    <description>Mitochondrial respiration will be measured by micropolarography.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Protein Concentration of Mitochondria</measure>
    <time_frame>Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation</time_frame>
    <description>Protein concentration will be determined 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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phosphorylation of proteins</measure>
    <time_frame>Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation</time_frame>
    <description>Phosphopeptides will be measured by mass spectrometry.</description>
  </secondary_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 lipid infusion 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 lipid infusion 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 lipid infusion and muscle biopsies.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lipid infusion and muscle biopsies</intervention_name>
    <description>Subjects will undergo a baseline muscle biopsy, a lipid infusion for 5 hours (60 ml/hr), and a muscle biopsy after the lipid infusion.</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>PI</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/NCT01724515
org study id: 11-006065 Aim 5
secondary id: R01DK066483
nct id: NCT01724515
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is determine if you have too much fat in your body that it will
      decrease the conversion of food energy into energy that your body can use.
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.

      The purpose of this study is to determine whether experimental lipid oversupply decreases
      mitochondrial respiratory function. We will use mitochondrial respiration studies in vitro
      and mass spectrometry and proteomics analysis to test the hypothesis that experimental lipid
      oversupply:

        1. Decreases mitochondrial respiration in response to lipid fuels.

        2. Reduces abundance of mitochondrial proteins.

        3. Alters phosphorylation of proteins in the electron transport chain.

      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 2 times. On study Day 1 subjects will be screened with
      a medical history and physical exam, and a 75 g oral glucose tolerance test, measure body fat
      percentage, and an electrocardiogram (EKG). On Study Day 2, subjects will report to the
      clinic after an overnight fast. Female subjects will take a urine pregnancy test. A muscle
      biopsy will be performed to take a small sample from one thigh. A lipid infusion will be
      performed for 5 hours (60 ml/hr), with blood samples taken at 8 intervals during the
      infusion. At the end of the 5 hour period, a second muscle biopsy will be taken from the
      other thigh. The fat infusion will stop, subjects will be given lunch and allowed to leave
      the clinic.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Mitochondrial Respiration
time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
description: Mitochondrial respiration will be measured by micropolarography.
measure: Protein Concentration of Mitochondria
time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
description: Protein concentration will be determined 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.
measure: Phosphorylation of proteins
time frame: Study Day 2, muscle biopsy approximately 6 hours after lipid infusion initiation
description: Phosphopeptides will be measured by mass spectrometry.
arm group label: Obese Non-Diabetic Subjects
arm group type: Experimental
description: All subjects on this arm will undergo lipid infusion and muscle biopsies.
arm group label: Type 2 Diabetic Subjects
arm group type: Experimental
description: All subjects on this arm will undergo lipid infusion and muscle biopsies.
arm group label: Healthy Control Subjects
arm group type: Experimental
description: All subjects on this arm will undergo lipid infusion and muscle biopsies.
intervention type: Other
intervention name: Lipid infusion and muscle biopsies
description: Subjects will undergo a baseline muscle biopsy, a lipid infusion for 5 hours (60 ml/hr), and a muscle biopsy after the lipid infusion.
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: PI
mesh term: Diabetes Mellitus