<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/NCT03032757</url>
  </required_header>
  <id_info>
    <org_study_id>RG_16-200</org_study_id>
    <nct_id>NCT03032757</nct_id>
  </id_info>
  <brief_title>Lysosomal Movement and Anabolic Resistance</brief_title>
  <official_title>Defining the Role of Lysosomal Movement in Age-associated Anabolic Resistance in Human Skeletal Muscle</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Birmingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Birmingham</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Age-associated loss of muscle mass, termed sarcopenia, is strongly associated with functional&#xD;
      impairment and physical disability in the elderly. Maintenance or growth of muscle mass is&#xD;
      mainly driven by increased muscle protein synthesis (i.e. the generation of new muscle&#xD;
      protein) in response to exercise and feeding. However, several investigations have shown that&#xD;
      elderly individuals have a blunted protein synthetic response following protein intake. This&#xD;
      inability of the elderly to properly respond to growth stimuli has been termed anabolic&#xD;
      resistance and plays a significant role in the development of sarcopenia. However, the&#xD;
      precise mechanisms underpinning anabolic resistance are unknown.&#xD;
&#xD;
      It is well established that muscle protein synthesis at the molecular level is regulated by a&#xD;
      cellular protein complex called mTORC1. When exposed to a growth stimulus, mTORC1 has been&#xD;
      shown to associate with lysosomes, i.e. the intracellular organelles responsible for the&#xD;
      breakdown of cellular proteins, and subsequently moving towards the cell periphery.&#xD;
&#xD;
      This movement of lysosome-associated mTORC1 within the cell is believed to be vital for the&#xD;
      activation of protein synthesis, as inhibition of lysosomal movement blunts mTORC1 activation&#xD;
      in response to amino acids. Thus, dysregulation of lysosomal movement in ageing muscle may&#xD;
      represent an underlying mechanism in the development of anabolic resistance. However, this&#xD;
      area of research is unexplored in the context of human skeletal muscle. The investigators&#xD;
      hypothesize that dysregulation of lysosomal movement plays a central role in the development&#xD;
      of age-associated skeletal muscle anabolic resistance.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 12, 2017</start_date>
  <completion_date type="Anticipated">August 30, 2018</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2018</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lysosomal movement</measure>
    <time_frame>~360 minutes</time_frame>
    <description>Changes in intracellular localization of lysosomes will be measured via immunofluorescence</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lysosomal movement in isolated muscle cells</measure>
    <time_frame>~30 minutes</time_frame>
    <description>Changes in intracellular localization of lysosomes will be measured via immunofluorescence</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">26</enrollment>
  <condition>Sarcopenia</condition>
  <arm_group>
    <arm_group_label>Resting leg of young males</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercising leg of young males</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Resting leg of elderly males</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercising leg of elderly males</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Essential amino acids</intervention_name>
    <description>240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.</description>
    <arm_group_label>Exercising leg of elderly males</arm_group_label>
    <arm_group_label>Exercising leg of young males</arm_group_label>
    <arm_group_label>Resting leg of elderly males</arm_group_label>
    <arm_group_label>Resting leg of young males</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Be a non-smoking male within the specified age range for each group (young; 18-35 yrs, old;&#xD;
        65-75 yrs)&#xD;
&#xD;
        Have a BMI (body mass index, body weight/height in m2) between 18 and 25 kg/m2, which is&#xD;
        considered a normal body mass index.&#xD;
&#xD;
        Be in good general health: no cardiovascular diseases or metabolic diseases.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Health problems such as: heart disease , metabolic disease such as phenylketonuria,&#xD;
        rheumatoid arthritis, uncontrolled hypertension, poor lung function, or any health&#xD;
        condition that might put the participant at risk when participating in this study.&#xD;
&#xD;
        Generalized neuromuscular disease (such as Parkinson's disease or motorneuron disease).&#xD;
&#xD;
        Involvement in regular structured resistance exercise training at the time of the study.&#xD;
&#xD;
        Consumption of any analgesic drugs, anti-inflammatory drugs, or medication that is known to&#xD;
        affect protein metabolism (beta-blockers, corticosteroids, NSAIDs).&#xD;
&#xD;
        Participants who have undergone muscle biopsy testing or isotope infusion procedures within&#xD;
        the last 5 years.&#xD;
&#xD;
        Allergic to lidocaine&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>William Apro, Ph.D.</last_name>
    <phone>01214142875</phone>
    <email>w.apro@bham.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Andrew Philp, Ph.D.</last_name>
    <phone>0121414 8872</phone>
    <email>a.philp@bham.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>School of Sport, Exercise and Rehabilitation Sciences at University of Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>West Midlands</state>
        <zip>B152TT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>William Apro, Ph.D.</last_name>
      <phone>0121 414 2875</phone>
      <email>w.apro@bham.ac.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>January 19, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>October 24, 2017</last_update_submitted>
  <last_update_submitted_qc>October 24, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 25, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Birmingham</investigator_affiliation>
    <investigator_full_name>William Apro</investigator_full_name>
    <investigator_title>Ph.D.</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcopenia</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/NCT03032757
org study id: RG_16-200
nct id: NCT03032757
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Age-associated loss of muscle mass, termed sarcopenia, is strongly associated with functional
      impairment and physical disability in the elderly. Maintenance or growth of muscle mass is
      mainly driven by increased muscle protein synthesis (i.e. the generation of new muscle
      protein) in response to exercise and feeding. However, several investigations have shown that
      elderly individuals have a blunted protein synthetic response following protein intake. This
      inability of the elderly to properly respond to growth stimuli has been termed anabolic
      resistance and plays a significant role in the development of sarcopenia. However, the
      precise mechanisms underpinning anabolic resistance are unknown.

      It is well established that muscle protein synthesis at the molecular level is regulated by a
      cellular protein complex called mTORC1. When exposed to a growth stimulus, mTORC1 has been
      shown to associate with lysosomes, i.e. the intracellular organelles responsible for the
      breakdown of cellular proteins, and subsequently moving towards the cell periphery.

      This movement of lysosome-associated mTORC1 within the cell is believed to be vital for the
      activation of protein synthesis, as inhibition of lysosomal movement blunts mTORC1 activation
      in response to amino acids. Thus, dysregulation of lysosomal movement in ageing muscle may
      represent an underlying mechanism in the development of anabolic resistance. However, this
      area of research is unexplored in the context of human skeletal muscle. The investigators
      hypothesize that dysregulation of lysosomal movement plays a central role in the development
      of age-associated skeletal muscle anabolic resistance.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Lysosomal movement
time frame: ~360 minutes
description: Changes in intracellular localization of lysosomes will be measured via immunofluorescence
measure: Lysosomal movement in isolated muscle cells
time frame: ~30 minutes
description: Changes in intracellular localization of lysosomes will be measured via immunofluorescence
arm group label: Resting leg of young males
arm group type: Experimental
arm group label: Exercising leg of young males
arm group type: Experimental
arm group label: Resting leg of elderly males
arm group type: Experimental
arm group label: Exercising leg of elderly males
arm group type: Experimental
intervention type: Dietary Supplement
intervention name: Essential amino acids
description: 240 mg essential amino acids per kg body weight dissolved in 500 ml of water provided after exercise.
arm group label: Exercising leg of elderly males
arm group label: Exercising leg of young males
arm group label: Resting leg of elderly males
arm group label: Resting leg of young males
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: William Apro, Ph.D.
phone: 01214142875
email: w.apro@bham.ac.uk
last name: Andrew Philp, Ph.D.
phone: 0121414 8872
email: a.philp@bham.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Birmingham
investigator full name: William Apro
investigator title: Ph.D.
mesh term: Sarcopenia