<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/NCT04500769</url>
  </required_header>
  <id_info>
    <org_study_id>43910</org_study_id>
    <secondary_id>3R01DK119619-02S1</secondary_id>
    <nct_id>NCT04500769</nct_id>
  </id_info>
  <brief_title>Training Induced Muscle Exosome Release</brief_title>
  <acronym>TIMER</acronym>
  <official_title>Exercise-induced Skeletal Muscle Exosomes Promote Adipocyte Lipolysis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>John McCarthy</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>University of Kentucky</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 primary objective of this study is to quantify miR-1 release from muscle in&#xD;
      extra-cellular vesicles following an acute resistance exercise bout and potential delivery to&#xD;
      subcutaneous adipose tissue in young healthy and obese adults.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Numerous studies in humans and animals have shown that aerobic exercise is beneficial to&#xD;
      adipose tissue function and whole-body metabolism. Both acute and chronic aerobic exercise&#xD;
      enhance adipocyte catecholamine sensitivity in humans and animals. Although relatively few&#xD;
      studies have investigated whether adipose adrenergic signaling is affected by resistance&#xD;
      exercise (RE), it is known that a single bout of RE can increase circulating NEFA and resting&#xD;
      energy expenditure and decrease respiratory quotient for up to 24 hours, indicative of&#xD;
      increased adipocyte lipolysis and muscle fatty acid oxidation. Furthermore, the lipolytic&#xD;
      response to RE is impaired in obese men. Using synergist ablation, a model of RE in mice, the&#xD;
      investigators show that adipose transcriptional responses are exosome-dependent, and that&#xD;
      serum exosomes enhance adipocyte catecholamine sensitivity and lipolysis for at least 24&#xD;
      hours. To the investigator's knowledge, this is the first demonstration of a potential&#xD;
      mechanism whereby RE imparts metabolic adaptations in adipose. Since adipose metabolic&#xD;
      function is crucial for determining whole-body metabolic outcomes, the ability of RE-induced&#xD;
      exosomes to improve adipose metabolism has significant clinical implications.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2019</start_date>
  <completion_date type="Actual">November 30, 2022</completion_date>
  <primary_completion_date type="Actual">November 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>miR-1 abundance</measure>
    <time_frame>90 minutes</time_frame>
    <description>Exosomal, muscle, and adipose miR-1 abundance will be quantified at baseline and following an acute bout of resistance exercise by qPCR. Primary miR-1A/B abundance in muscle and adipose will also be quantified by qPCR. Mir-1 and primary miR-1A/B abundance will be normalized to U6 RNA or Rpl38 abundance,respectively, with normalized expression presented in arbitrary units.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Metabolism</condition>
  <arm_group>
    <arm_group_label>Acute Resistance Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will perform four exercises: squat, knee extension, leg press, and lat pulldown at 80% of 1-RM determined during a previous visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Acute Resistance Exercise</intervention_name>
    <description>Participants will perform three sets of eight repetitions, with a 90-120 second rest between sets, with a fourth set performed to failure. All resistance exercise will be performed on pneumatic resistance devices (Keiser Sports Health Equipment, Fresno, CA).</description>
    <arm_group_label>Acute Resistance Exercise</arm_group_label>
    <other_name>Strength Training</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-30 years of age.&#xD;
&#xD;
          -  Either BMI &lt;25 or &gt;30.&#xD;
&#xD;
          -  Relatively sedentary, reporting no participation in regular (&gt;1 day per week) exercise&#xD;
             for at least the past 3 months.&#xD;
&#xD;
          -  Non-smoker.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI between 25 and 30.&#xD;
&#xD;
          -  Evidence or signs and symptoms for cardiovascular disease (previous heart attack,&#xD;
             arrhythmias, angina, shortness of breath, extreme fatigue, unusual pain in neck, jaw,&#xD;
             throat, upper abdomen, or back, swelling in feet, legs, or ankles).&#xD;
&#xD;
          -  Evidence or signs and symptoms of metabolic syndrome or disorder (diagnosis of&#xD;
             diabetes or insulin resistance, elevated BP, high fasting blood sugar, abnormal&#xD;
             cholesterol or triglyceride levels).&#xD;
&#xD;
          -  Chronic aspirin or NSAID use (unless it can be safely stopped prior to the biopsies),&#xD;
             and any other use of an anticoagulant (e.g., Coumadin) or history of bleeding&#xD;
             including history of hypo- or hyper-coagulation disorders.&#xD;
&#xD;
          -  Neurological, musculoskeletal, or other disorder that would preclude safe&#xD;
             participation in the weight lifting tasks and all performance tests.&#xD;
&#xD;
          -  Any other medical condition that would interfere with testing or increase one's risk&#xD;
             of complications during exercise, as judged by the study physician.&#xD;
&#xD;
          -  Any other condition or events considered exclusionary by the PI and/or physician, such&#xD;
             as non-compliance.&#xD;
&#xD;
          -  Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy&#xD;
             procedure).&#xD;
&#xD;
          -  Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John McCarthy, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>August 3, 2023</last_update_submitted>
  <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>John McCarthy</investigator_full_name>
    <investigator_title>Associate Professor, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Metabolism</keyword>
  <keyword>Muscle</keyword>
  <keyword>Extracellular Vesicles</keyword>
  <keyword>Exosomes</keyword>
  <keyword>Resistance Exercise</keyword>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 17, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/69/NCT04500769/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04500769
org study id: 43910
secondary id: 3R01DK119619-02S1
nct id: NCT04500769
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to quantify miR-1 release from muscle in
      extra-cellular vesicles following an acute resistance exercise bout and potential delivery to
      subcutaneous adipose tissue in young healthy and obese adults.
Numerous studies in humans and animals have shown that aerobic exercise is beneficial to
      adipose tissue function and whole-body metabolism. Both acute and chronic aerobic exercise
      enhance adipocyte catecholamine sensitivity in humans and animals. Although relatively few
      studies have investigated whether adipose adrenergic signaling is affected by resistance
      exercise (RE), it is known that a single bout of RE can increase circulating NEFA and resting
      energy expenditure and decrease respiratory quotient for up to 24 hours, indicative of
      increased adipocyte lipolysis and muscle fatty acid oxidation. Furthermore, the lipolytic
      response to RE is impaired in obese men. Using synergist ablation, a model of RE in mice, the
      investigators show that adipose transcriptional responses are exosome-dependent, and that
      serum exosomes enhance adipocyte catecholamine sensitivity and lipolysis for at least 24
      hours. To the investigator's knowledge, this is the first demonstration of a potential
      mechanism whereby RE imparts metabolic adaptations in adipose. Since adipose metabolic
      function is crucial for determining whole-body metabolic outcomes, the ability of RE-induced
      exosomes to improve adipose metabolism has significant clinical implications.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: miR-1 abundance
time frame: 90 minutes
description: Exosomal, muscle, and adipose miR-1 abundance will be quantified at baseline and following an acute bout of resistance exercise by qPCR. Primary miR-1A/B abundance in muscle and adipose will also be quantified by qPCR. Mir-1 and primary miR-1A/B abundance will be normalized to U6 RNA or Rpl38 abundance,respectively, with normalized expression presented in arbitrary units.
arm group label: Acute Resistance Exercise
arm group type: Experimental
description: Participants will perform four exercises: squat, knee extension, leg press, and lat pulldown at 80% of 1-RM determined during a previous visit.
intervention type: Behavioral
intervention name: Acute Resistance Exercise
description: Participants will perform three sets of eight repetitions, with a 90-120 second rest between sets, with a fourth set performed to failure. All resistance exercise will be performed on pneumatic resistance devices (Keiser Sports Health Equipment, Fresno, CA).
arm group label: Acute Resistance Exercise
other name: Strength Training
criteria: 
gender: All
minimum age: 18 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: John McCarthy, Ph.D.
role: Principal Investigator
affiliation: University of Kentucky
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: John McCarthy
investigator title: Associate Professor, Principal Investigator
provided document: 