<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/NCT02230839</url>
  </required_header>
  <id_info>
    <org_study_id>TRIMDFH 500423</org_study_id>
    <nct_id>NCT02230839</nct_id>
    <nct_alias>NCT01808924</nct_alias>
  </id_info>
  <brief_title>Muscle Insulin Resistance in Aging (Mirage)</brief_title>
  <official_title>Muscle Insulin Resistance In Aging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AdventHealth Translational Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AdventHealth Translational Research Institute</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to provide information regarding potential factors underlying&#xD;
      metabolic dysfunction, insulin resistance, and loss of muscle mass in aging muscle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Objectives:&#xD;
&#xD;
        1. To determine the effects of diet-induced weight loss with and without the addition of&#xD;
           exercise on mitochondrial biogenesis and energetic capacity, cellular redox state and&#xD;
           insulin resistance.&#xD;
&#xD;
        2. To determine the effects of diet-induced weight loss with and without the addition of&#xD;
           exercise on intramyocellular lipid profiles.&#xD;
&#xD;
        3. To determine the effects of diet-induced weight loss with and without exercise on&#xD;
           skeletal muscle proteins mediating a program of autophagy and either loss or maintenance&#xD;
           of muscle mass.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 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>Measure of intramyocellular lipids</measure>
    <time_frame>Visit 3 ~22 hours</time_frame>
    <description>A percutaneous muscle biopsy of the vastus lateralis will be obtained, and the intramyocellular lipids will be measured by high-performance liquid chromatography-tandem mass spectrometry.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measure of insulin sensitivity</measure>
    <time_frame>Visit 3 ~22 hours</time_frame>
    <description>Insulin sensitivity will be measured using an intravenous catheter (glucose clamps) that will be placed in the antecubital vein for subsequent insulin and glucose infusions and for stable isotope infusions. This will measure insulin-stimulated changes in insulin signaling proteins and metabolism.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Measure muscle strength and power</measure>
    <time_frame>Visit 2 (baseline) and 6 months</time_frame>
    <description>Muscle strength and power will be measured in participants who have successfully completed all screening procedures.&#xD;
Measurement is obtained using a short physical performance battery, knee extension, and muscle power testing using a pneumatic-driven dynamometer.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Sarcopenia</condition>
  <arm_group>
    <arm_group_label>Exercise training protocol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Energy restriction-induced weight loss</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Health Education</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Participants will complete a progressive 6-month exercise training program, 4-5 days per week, 45 min per session (180 min per week), consisting mostly of walking (both outside and on an indoor treadmill) but with the option to include stationary cycling, elliptical and rowing machines, similar to what we have utilized previously to elicit significant improvements in insulin sensitivity in both middle-age and older adults (52-55). Beginning at week 8, these subjects will also perform 2 non-consecutive resistance exercise sessions per week, 30 min per session, focused on major muscle groups using resistance machines (total days of exercise will still be 4 to 5).</description>
    <arm_group_label>Exercise training protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Energy Restriction-Induced Weight Loss</intervention_name>
    <description>The goal of the weight loss intervention will be to produce a weight loss of 10% body weight. A reduction of 500-1000 kcal/day - based on baseline weight -and low fat (&lt;30% of calories from fat) diet will be used as part of the weight loss intervention.</description>
    <arm_group_label>Energy restriction-induced weight loss</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  65-80 years of age&#xD;
&#xD;
          -  Stable weight (No Gain/Loss of &gt;10 lbs in 6 months)&#xD;
&#xD;
          -  Sedentary (≤ 1 continuous exercise/week)&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  BMI ≥ 30 kg/m2&#xD;
&#xD;
          -  Resting Blood Pressure ≤ 150 millimeters of mercury systolic and ≤ 95 millimeters of&#xD;
             mercury diastolic&#xD;
&#xD;
          -  Note from Primary care physician/Cardiologist for exercise clearance if positive&#xD;
             stress test symptoms were observed from exercise test&#xD;
&#xD;
          -  Must be willing to washout for 14 days from all diabetes medication and independent in&#xD;
             self blood glucose monitoring during the washout periods (those with diabetes only)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant cardiovascular disease including history of myocardial&#xD;
             infarction, within the past year&#xD;
&#xD;
          -  Peripheral Vascular Disease&#xD;
&#xD;
          -  Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease&#xD;
&#xD;
          -  Clinically diminished pulse&#xD;
&#xD;
          -  Presence of bruits in lower extremities&#xD;
&#xD;
          -  Previous history of pulmonary emboli&#xD;
&#xD;
          -  Peripheral Neuropathy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bret Goodpaster, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Translational Research Institute for Metabolism and Diabetes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Translational Research Institute for Metabolism and Diabetes</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.tri-md.org</url>
    <description>Florida Hospital Translational Research Institute for Metabolism and Diabetes</description>
  </link>
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  <verification_date>July 2023</verification_date>
  <study_first_submitted>August 7, 2014</study_first_submitted>
  <study_first_submitted_qc>August 29, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2014</study_first_posted>
  <last_update_submitted>July 21, 2023</last_update_submitted>
  <last_update_submitted_qc>July 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>insulin resistance</keyword>
  <keyword>muscle</keyword>
  <keyword>health education</keyword>
  <keyword>exercise</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcopenia</mesh_term>
    <mesh_term>Insulin Resistance</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/NCT02230839
org study id: TRIMDFH 500423
nct id: NCT02230839
nct alias: NCT01808924
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to provide information regarding potential factors underlying
      metabolic dysfunction, insulin resistance, and loss of muscle mass in aging muscle.
Study Objectives:

        1. To determine the effects of diet-induced weight loss with and without the addition of
           exercise on mitochondrial biogenesis and energetic capacity, cellular redox state and
           insulin resistance.

        2. To determine the effects of diet-induced weight loss with and without the addition of
           exercise on intramyocellular lipid profiles.

        3. To determine the effects of diet-induced weight loss with and without exercise on
           skeletal muscle proteins mediating a program of autophagy and either loss or maintenance
           of muscle mass.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Measure of intramyocellular lipids
time frame: Visit 3 ~22 hours
description: A percutaneous muscle biopsy of the vastus lateralis will be obtained, and the intramyocellular lipids will be measured by high-performance liquid chromatography-tandem mass spectrometry.
measure: Measure of insulin sensitivity
time frame: Visit 3 ~22 hours
description: Insulin sensitivity will be measured using an intravenous catheter (glucose clamps) that will be placed in the antecubital vein for subsequent insulin and glucose infusions and for stable isotope infusions. This will measure insulin-stimulated changes in insulin signaling proteins and metabolism.
measure: Measure muscle strength and power
time frame: Visit 2 (baseline) and 6 months
description: Muscle strength and power will be measured in participants who have successfully completed all screening procedures.
Measurement is obtained using a short physical performance battery, knee extension, and muscle power testing using a pneumatic-driven dynamometer.
arm group label: Exercise training protocol
arm group type: Experimental
arm group label: Energy restriction-induced weight loss
arm group type: Experimental
arm group label: Health Education
arm group type: No Intervention
intervention type: Behavioral
intervention name: Exercise
description: Participants will complete a progressive 6-month exercise training program, 4-5 days per week, 45 min per session (180 min per week), consisting mostly of walking (both outside and on an indoor treadmill) but with the option to include stationary cycling, elliptical and rowing machines, similar to what we have utilized previously to elicit significant improvements in insulin sensitivity in both middle-age and older adults (52-55). Beginning at week 8, these subjects will also perform 2 non-consecutive resistance exercise sessions per week, 30 min per session, focused on major muscle groups using resistance machines (total days of exercise will still be 4 to 5).
arm group label: Exercise training protocol
intervention type: Behavioral
intervention name: Energy Restriction-Induced Weight Loss
description: The goal of the weight loss intervention will be to produce a weight loss of 10% body weight. A reduction of 500-1000 kcal/day - based on baseline weight -and low fat (<30% of calories from fat) diet will be used as part of the weight loss intervention.
arm group label: Energy restriction-induced weight loss
criteria: 
gender: All
minimum age: 65 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bret Goodpaster, PhD
role: Principal Investigator
affiliation: Translational Research Institute for Metabolism and Diabetes
facility: 
country: United States
url: http://www.tri-md.org
description: Florida Hospital Translational Research Institute for Metabolism and Diabetes
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responsible party type: Sponsor
mesh term: Sarcopenia
mesh term: Insulin Resistance