<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/NCT02999802</url>
  </required_header>
  <id_info>
    <org_study_id>15-0226</org_study_id>
    <secondary_id>R56AG051267</secondary_id>
    <nct_id>NCT02999802</nct_id>
  </id_info>
  <brief_title>Nutrient Sensing &amp; Signaling in Aging Muscle</brief_title>
  <official_title>Nutrient Sensing &amp; Signaling in Aging Muscle</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Texas Medical Branch, Galveston</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Texas Medical Branch, Galveston</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research seeks to better understand how cellular and molecular bases of changes&#xD;
      associated with aging contribute to decreased function and increased incidence of disease.&#xD;
      Specific mechanism in muscle responsible for anabolic resistance - a key component of&#xD;
      sarcopenia and frailty - will be identified. The proposed research is relevant to public&#xD;
      health because the discovery of new targets for interventions and novel therapeutics to&#xD;
      improve muscle strength and function, prevent falls, and reduce physical dependency will&#xD;
      improve the healthspan and quality of life in older adults by improving their physical&#xD;
      function and ability to remain independent and healthy for a longer period of time.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Anabolic resistance to nutrition is the reduced ability of skeletal muscle to increase&#xD;
      protein synthesis in response to feeding. It is a major contributor to muscle atrophy in&#xD;
      aging, inactivity, burns, trauma, and cancer cachexia. The effects of anabolic resistance on&#xD;
      health and physical function are important. For example, the loss of muscle mass and strength&#xD;
      with aging (sarcopenia) increases the risk for falls, physical dependency and morbidity in&#xD;
      older adults. A major determinant of muscle size is muscle protein content, which is&#xD;
      controlled by the fine balance between protein synthesis and breakdown. Recently,&#xD;
      investigators have found that amino acids and exercise independently increase muscle protein&#xD;
      synthesis and overall anabolism by activating the mammalian/mechanistic target of rapamycin&#xD;
      complex 1 (mTORC1) signaling pathway in humans. Aging and inactivity reduce these anabolic&#xD;
      effects, but the underlying mechanisms of anabolic resistance are not known. The purpose of&#xD;
      this application is to better understand how anabolic resistance develops in skeletal muscle.&#xD;
      The long-term goal is to identify specific molecular targets for the development of&#xD;
      evidence-based clinical interventions to counteract anabolic resistance and muscle wasting in&#xD;
      clinical populations. Here, investigators will focus on one potential mechanisms underlying&#xD;
      anabolic resistance to amino acids: activation of mTORC1 in human muscle cells. The central&#xD;
      hypothesis is that the physical activity restores mTORC1 signaling which is the primary&#xD;
      contributor to anabolic resistance in human skeletal muscle. Investigators will test this&#xD;
      hypothesis in healthy subjects with the following specific aim: Determine the effect of&#xD;
      increasing habitual physical activity on anabolic resistance. Investigators will study human&#xD;
      subjects utilizing stable isotopes model to measure amino acid kinetics and muscle protein&#xD;
      metabolism in combination with molecular analysis of muscle to determine the regulatory role&#xD;
      of amino acids, physical inactivity, and amino acid transporter functional activity on&#xD;
      mTORC1. The proposed approach is innovative because it represents a new and substantial&#xD;
      departure from the status quo as investigators will examine the underlying mechanisms of&#xD;
      anabolic resistance to nutrition using novel methodological approaches. The proposed research&#xD;
      is significant because it will lead to the development of evidence-based interventions to&#xD;
      treat sarcopenia and muscle wasting.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2015</start_date>
  <completion_date type="Actual">December 21, 2016</completion_date>
  <primary_completion_date type="Actual">December 21, 2016</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in muscle protein synthesis in response to amino acids</measure>
    <time_frame>Change from baseline to 3 months</time_frame>
    <description>Measurement of the change in muscle protein synthesis in response to amino acids by standard stable isotope method</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Muscle mass</measure>
    <time_frame>Change from baseline to 3 months</time_frame>
    <description>Measurement in the change in muscle mass by DEXA scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle function</measure>
    <time_frame>Change from baseline to 3 months</time_frame>
    <description>Measurement of the change in muscle function by standard methods</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Nutrient Sensing</condition>
  <arm_group>
    <arm_group_label>Exercise</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Determining the effect of 12 weeks of resistance training exercise on the response of muscle amino acid sensing</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>Progressive resistance exercise training</description>
    <arm_group_label>Exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  65-80 yrs&#xD;
&#xD;
          -  Stable body weight for at least 1 year&#xD;
&#xD;
          -  Ability to sign consent form:&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exercise training (&gt;2 weekly sessions of moderate to high intensity aerobic or&#xD;
             resistance exercise)&#xD;
&#xD;
          -  Physical dependence or frailty (impairment in the Activities of Daily Living (ADL),&#xD;
             history of falls (&gt;2/year), or &gt;5% weight loss in the past year)&#xD;
&#xD;
          -  Significant heart, liver, kidney, blood, or respiratory disease&#xD;
&#xD;
          -  Peripheral vascular disease&#xD;
&#xD;
          -  Diabetes mellitus or other untreated endocrine disease&#xD;
&#xD;
          -  Active cancer&#xD;
&#xD;
          -  Acute infectious disease or history of chronic infections&#xD;
&#xD;
          -  Recent (within 3 months) treatment with anabolic steroids, or prolonged systemic&#xD;
             corticosteroids.&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Tobacco use (smoking or chewing)&#xD;
&#xD;
          -  Malnutrition (BMI &lt; 18.5 kg/sq meter)&#xD;
&#xD;
          -  Obesity (BMI &gt; 30 kg/sq meter)&#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>Blake B Rasmussen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UTMB</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>June 11, 2018</last_update_submitted>
  <last_update_submitted_qc>June 11, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nutrient Sensing</keyword>
  <keyword>Exercise</keyword>
  <keyword>Elderly</keyword>
  <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/NCT02999802
org study id: 15-0226
secondary id: R56AG051267
nct id: NCT02999802
lead sponsor: 
collaborator: 
has dmc: Yes
This research seeks to better understand how cellular and molecular bases of changes
      associated with aging contribute to decreased function and increased incidence of disease.
      Specific mechanism in muscle responsible for anabolic resistance - a key component of
      sarcopenia and frailty - will be identified. The proposed research is relevant to public
      health because the discovery of new targets for interventions and novel therapeutics to
      improve muscle strength and function, prevent falls, and reduce physical dependency will
      improve the healthspan and quality of life in older adults by improving their physical
      function and ability to remain independent and healthy for a longer period of time.
Anabolic resistance to nutrition is the reduced ability of skeletal muscle to increase
      protein synthesis in response to feeding. It is a major contributor to muscle atrophy in
      aging, inactivity, burns, trauma, and cancer cachexia. The effects of anabolic resistance on
      health and physical function are important. For example, the loss of muscle mass and strength
      with aging (sarcopenia) increases the risk for falls, physical dependency and morbidity in
      older adults. A major determinant of muscle size is muscle protein content, which is
      controlled by the fine balance between protein synthesis and breakdown. Recently,
      investigators have found that amino acids and exercise independently increase muscle protein
      synthesis and overall anabolism by activating the mammalian/mechanistic target of rapamycin
      complex 1 (mTORC1) signaling pathway in humans. Aging and inactivity reduce these anabolic
      effects, but the underlying mechanisms of anabolic resistance are not known. The purpose of
      this application is to better understand how anabolic resistance develops in skeletal muscle.
      The long-term goal is to identify specific molecular targets for the development of
      evidence-based clinical interventions to counteract anabolic resistance and muscle wasting in
      clinical populations. Here, investigators will focus on one potential mechanisms underlying
      anabolic resistance to amino acids: activation of mTORC1 in human muscle cells. The central
      hypothesis is that the physical activity restores mTORC1 signaling which is the primary
      contributor to anabolic resistance in human skeletal muscle. Investigators will test this
      hypothesis in healthy subjects with the following specific aim: Determine the effect of
      increasing habitual physical activity on anabolic resistance. Investigators will study human
      subjects utilizing stable isotopes model to measure amino acid kinetics and muscle protein
      metabolism in combination with molecular analysis of muscle to determine the regulatory role
      of amino acids, physical inactivity, and amino acid transporter functional activity on
      mTORC1. The proposed approach is innovative because it represents a new and substantial
      departure from the status quo as investigators will examine the underlying mechanisms of
      anabolic resistance to nutrition using novel methodological approaches. The proposed research
      is significant because it will lead to the development of evidence-based interventions to
      treat sarcopenia and muscle wasting.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in muscle protein synthesis in response to amino acids
time frame: Change from baseline to 3 months
description: Measurement of the change in muscle protein synthesis in response to amino acids by standard stable isotope method
measure: Muscle mass
time frame: Change from baseline to 3 months
description: Measurement in the change in muscle mass by DEXA scan
measure: Muscle function
time frame: Change from baseline to 3 months
description: Measurement of the change in muscle function by standard methods
arm group label: Exercise
arm group type: Experimental
description: Determining the effect of 12 weeks of resistance training exercise on the response of muscle amino acid sensing
intervention type: Behavioral
intervention name: Exercise
description: Progressive resistance exercise training
arm group label: Exercise
criteria: 
gender: All
minimum age: 65 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Blake B Rasmussen, PhD
role: Principal Investigator
affiliation: University of Texas
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No