xml: <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/NCT05997095</url>
    </required_header>
    <id_info>
      <org_study_id>FMHS 261-0423</org_study_id>
      <nct_id>NCT05997095</nct_id>
    </id_info>
    <brief_title>Post-operative Electrical Muscle Stimulation to Stimulate Muscle Protein Synthesis in Humans</brief_title>
    <acronym>PoEMS</acronym>
    <official_title>Optimisation of Post-operative Electrical Muscle Stimulation (PoEMS) to Stimulate Muscle Protein Synthesis in Humans</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Nottingham</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Nottingham</source>
    <oversight_info>
      <has_dmc>No</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>
        Skeletal muscle accounts for approximately 45-55% of total body mass in healthy adults and&#xD;
        plays a pivotal role in whole-body metabolic health, locomotion and physical independence.&#xD;
        Undesirable loss of skeletal muscle mass (atrophy) is, however, a common feature of many&#xD;
        communicable and non-communicable diseases including ageing, bed-rest/immobilisation, cancer&#xD;
        and physical inactivity. As such, the design of optimal strategies (e.g., different types of&#xD;
        exercise) to &quot;offset&quot; these detrimental losses of muscle is a focus for both researchers and&#xD;
        clinicians.&#xD;
  &#xD;
        One situation where losses of muscle mass occur very quickly (i.e., within a few days) is&#xD;
        after surgery. However, at this time, most people (especially if they have had major&#xD;
        abdominal or lower-limb surgery) are not able to perform exercise and as such a different&#xD;
        strategy to maintain muscle mass needs to be found. It has been shown that electrical&#xD;
        stimulation of the leg muscles can maintain muscle mass and function in patients after&#xD;
        surgery. It is not however yet known, what the optimal electrical stimulation regime is to&#xD;
        preserve muscle mass during situations of disuse.&#xD;
  &#xD;
        This study aims to examine the impact of three different electrical stimulation protocols on&#xD;
        muscle building processes in individuals age-matched to those most commonly presenting for&#xD;
        major abdominal surgery. This information will then be used in a clinical trial of surgical&#xD;
        patients to see if it can preserve their muscle mass and function in the post-operative&#xD;
        period.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The contraction of skeletal muscles depends on the regulation of the nervous system and the&#xD;
        coordination of neuromuscular function. The smallest motor nervous system associated with&#xD;
        muscle contraction is the motor unit (MU), which consists of an efferent motor neuron and all&#xD;
        of the muscle fibres it innervates. Muscle tissue also undergoes adaptive alternations in&#xD;
        response to external stimuli, such as the gradual decline in muscle mass and strength during&#xD;
        ageing, and atrophy following muscle disuse. A number of studies have demonstrated that&#xD;
        different types of voluntary movements, such as resistance exercise training (RET), can&#xD;
        prevent or attenuate such alternations to a certain extent via increases in muscle protein&#xD;
        synthesis (MPS).&#xD;
  &#xD;
        However, certain situations such as post-operative bed rest render RET interventions an&#xD;
        unachievable option. Neuromuscular electrical stimulation (NMES) can be applied as a&#xD;
        surrogate; acting to evoke involuntary contraction of the target muscles via electrical&#xD;
        current applied to the muscle belly. Although NMES stimulation has been widely tested in the&#xD;
        intensive care environment, results have shown variable efficacy- perhaps due to the&#xD;
        multi-organ failure and associated catabolic systemic environment encountered by the majority&#xD;
        of these patients.&#xD;
  &#xD;
        It has recently shown that in post-operative abdominal surgery patients, 5-days of NMES,&#xD;
        performed at frequency of 30 Hz in a 1 second &quot;on&quot;, 1 second &quot;off&quot; contraction pattern, can&#xD;
        mitigate losses in muscle mass and function. However, this study 'borrowed' a protocol from&#xD;
        previous intensive care literature, and as such may not be optimal with regards to frequency&#xD;
        or contraction pattern. Given that this protocol was highly tolerated by patients in a&#xD;
        previous study (i.e., based on 30 min of daily NMES, patients in this study said they would&#xD;
        tolerate it for 45 to 240 (mean 90) min), it is plausible that higher frequency NMES (~100&#xD;
        Hz), enabling greater force production may be both viable and result in further mitigation of&#xD;
        muscle mass and function losses. It has also been demonstrated that the time muscle is under&#xD;
        loaded tension during RET may be an important modulator of MPS and subsequent gains in muscle&#xD;
        mass. Therefore, increasing the contraction relative to relaxation time during NMES (e.g., 3&#xD;
        seconds on, 1 second off) may be another feasible and perhaps more beneficial strategy to&#xD;
        reduce muscle mass losses in populations where an increase in frequency may not be possible&#xD;
        or tolerable.&#xD;
  &#xD;
        Knowing that muscle maintenance is based on a dynamic equilibrium between MPS and muscle&#xD;
        protein breakdown, the impact of different NMES protocols on MPS, associated cell signalling,&#xD;
        and nutrient delivery pathways needs to be explored so that an optimal intervention can be&#xD;
        tested in clinical settings associated with disuse atrophy. To date, no previous studies have&#xD;
        compared differing frequencies of NMES on the muscle metabolic responses in older adults, nor&#xD;
        the effect of differing NMES-induced contraction patterns.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 22, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 28, 2025</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>Crossover Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Skeletal Muscle Protein Synthesis</measure>
      <time_frame>4 hours</time_frame>
      <description>A primed continuous infusion of a stable isotope tracer (1,2 13C2] leucine) will be initiated (Prime: 0.7 mg/kg; Constant: 1.0 mg/kg/h) at time 0h. After 60 min of stable isotope infusion, a single muscle biopsy will be taken from one leg. Another biopsy from the same leg will be taken 120 min later, and a third 240 min after the second to provide rates of muscle protein synthesis in the rested condition and in response to NMES, respectively. The fractional synthetic rate (FSR) of the myofibrillar fraction was calculated from the incorporation of [1,2 13C2] leucine, using venous plasma labelling between muscle biopsies to represent the immediate precursor for protein synthesis. This will give a rate (%/hour) of muscle protein synthesis.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Skeletal Muscle Anabolic Signalling</measure>
      <time_frame>4 hours</time_frame>
      <description>Total and phosphorylation of established anabolic proteins in human skeletal muscle will be quantified via Western Blotting.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Skeletal Muscle Blood Flow</measure>
      <time_frame>Baseline and 30 minutes post neuromuscular stimulation</time_frame>
      <description>Contrast enhanced ultrasound (CEUS) measurements will be made 60 min before the NMES and 30 min after. To achieve this, a custom-made probe holder will be placed on the leg to be stimulated at the start of the study. For each measurement, Sonovue will be infused at 2ml/min for 1 minute and then 1ml/min for 30 sec to achieve systemic steady state, with a continued infusion at 1ml/min for the duration of the measurements. Each measurement will include three, 30-second capture-flash cycles which will form a Sonovue replenishment curve for the portion of vastus lateralis muscle (VL) under the probe. blood flow will be calculated by measuring the reperfusion rate of the microbubbles in the muscle microvasculature following destruction with a high mechanical index flash, given the infusion of contrast is continuous.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Perceived discomfort of Neuromuscular Electrical stimulation</measure>
      <time_frame>Immediately post neuromuscular stimulation</time_frame>
      <description>At the end of the NMES, participants will be asked to rate the perceived discomfort on a Likert scale of 1-10 and respond to the question of &quot;that stimulation was 30-minutes, how much longer would you have been willing to have stimulation for if you were in bed recovering from an injury or illness i.e., it was not interfering with your ability to perform other activities?&quot;</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Skeletal Muscle Atrophy</condition>
    <arm_group>
      <arm_group_label>30Hz (low-intensity)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Volunteers receive 30 mins of neuromuscular electrical stimulation at 30Hz with a contraction pattern of 1 second &quot;on&quot; and 1 second &quot;off&quot;</description>
    </arm_group>
    <arm_group>
      <arm_group_label>100Hz (higher-intensity)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Volunteers receive 30 mins of neuromuscular electrical stimulation at 100Hz with a contraction pattern of 1 second &quot;on&quot; and 1 second &quot;off&quot;</description>
    </arm_group>
    <arm_group>
      <arm_group_label>30Hz (low-intensity, 3:1)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Volunteers receive 30 mins of neuromuscular electrical stimulation at 30Hz with a contraction pattern of 3 seconds &quot;on&quot; and 1 second &quot;off&quot;</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Neuromuscular electrical stimulation (NMES/0</intervention_name>
      <description>NMES will be applied for 30 min and will be delivered using an approved, CE-marked device (Premier Combo Plus, Med-Fit Ltd, UK) using two large (7.5 × 13 cm) electrodes placed proximally and distally over the lateral quadriceps. The set protocols will be pre-programmed into to the device and the amplitude value will match the setting that was determined during a familiarisation visit</description>
      <arm_group_label>100Hz (higher-intensity)</arm_group_label>
      <arm_group_label>30Hz (low-intensity)</arm_group_label>
      <arm_group_label>30Hz (low-intensity, 3:1)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged 60-85 y&#xD;
  &#xD;
            -  Willing and able to give informed consent for participation in the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  BMI &lt;18.5 or &gt;35kg/m2&#xD;
  &#xD;
            -  Participation in any regular, structured RET within the past 6 months&#xD;
  &#xD;
            -  Musculoskeletal disorders&#xD;
  &#xD;
            -  Severe respiratory disease:&#xD;
  &#xD;
            -  COPD&#xD;
  &#xD;
            -  Pulmonary hypertension&#xD;
  &#xD;
            -  Neurological disorders:&#xD;
  &#xD;
            -  Cerebrovascular disease (cerebral haemorrhage; cerebral ischemic stroke)&#xD;
  &#xD;
            -  Intracranial space-occupying lesion&#xD;
  &#xD;
            -  Epilepsy&#xD;
  &#xD;
            -  Metabolic disease:&#xD;
  &#xD;
            -  Hyper and hypo parathyroidism&#xD;
  &#xD;
            -  Untreated hyper and hypothyroidism&#xD;
  &#xD;
            -  Cushing's disease&#xD;
  &#xD;
            -  Type 1 or 2 diabetes&#xD;
  &#xD;
            -  Active cardiovascular problems:&#xD;
  &#xD;
            -  Uncontrolled hypertension (BP&gt;160/100mmHg)&#xD;
  &#xD;
            -  Recent cardiac event&#xD;
  &#xD;
            -  Heart failure (Class III/IV)&#xD;
  &#xD;
            -  Arrhythmia&#xD;
  &#xD;
            -  Angina&#xD;
  &#xD;
            -  Blood clotting disorders&#xD;
  &#xD;
            -  Active inflammatory bowel or renal disease&#xD;
  &#xD;
            -  Recent malignancy (in previous 3 years)&#xD;
  &#xD;
            -  Recent steroid treatment within 6 months or hormone replacement therapy&#xD;
  &#xD;
            -  Family history of early (&lt;55yrs) death from cardiovascular disease&#xD;
  &#xD;
            -  Known sensitivity to Sonovue&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>60 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Bethan Phillips, PhD</last_name>
      <phone>01332 724676</phone>
      <email>beth.phillips@nottingham.ac.uk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Mathew Piasecki, PhD</last_name>
      <phone>01332 724688</phone>
      <email>Mathew.Piasecki@nottingham.ac.uk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Nottingham</name>
        <address>
          <city>Nottingham</city>
          <state>Nottinghamshire</state>
          <zip>NG7 2RD</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Bethan Phillips, PhD</last_name>
        <phone>01332 724676</phone>
        <email>beth.phillips@nottingham.ac.uk</email>
      </contact>
      <contact_backup>
        <last_name>Mathew Piasecki, PhD</last_name>
        <phone>01332 724688</phone>
        <email>Mathew.Piasecki@nottingham.ac.uk</email>
      </contact_backup>
      <investigator>
        <last_name>Philip Atherton, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Kenneth Smith, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Daniel Wilkinson, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jon Lund, M.D</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <reference>
      <citation>Hardy EJ, Hatt J, Doleman B, Smart TF, Piasecki M, Lund JN, Phillips BE. Post-operative electrical muscle stimulation attenuates loss of muscle mass and function following major abdominal surgery in older adults: a split body randomised control trial. Age Ageing. 2022 Oct 6;51(10):afac234. doi: 10.1093/ageing/afac234.</citation>
      <PMID>36315433</PMID>
    </reference>
    <reference>
      <citation>Hardy EJO, Inns TB, Hatt J, Doleman B, Bass JJ, Atherton PJ, Lund JN, Phillips BE. The time course of disuse muscle atrophy of the lower limb in health and disease. J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2616-2629. doi: 10.1002/jcsm.13067. Epub 2022 Sep 14.</citation>
      <PMID>36104842</PMID>
    </reference>
    <reference>
      <citation>Wall BT, Dirks ML, Verdijk LB, Snijders T, Hansen D, Vranckx P, Burd NA, Dendale P, van Loon LJ. Neuromuscular electrical stimulation increases muscle protein synthesis in elderly type 2 diabetic men. Am J Physiol Endocrinol Metab. 2012 Sep 1;303(5):E614-23. doi: 10.1152/ajpendo.00138.2012. Epub 2012 Jun 26.</citation>
      <PMID>22739107</PMID>
    </reference>
    <reference>
      <citation>Mancinelli R, Toniolo L, Di Filippo ES, Doria C, Marrone M, Maroni CR, Verratti V, Bondi D, Maccatrozzo L, Pietrangelo T, Fulle S. Neuromuscular Electrical Stimulation Induces Skeletal Muscle Fiber Remodeling and Specific Gene Expression Profile in Healthy Elderly. Front Physiol. 2019 Nov 27;10:1459. doi: 10.3389/fphys.2019.01459. eCollection 2019.</citation>
      <PMID>31827446</PMID>
    </reference>
    <reference>
      <citation>Burd NA, Andrews RJ, West DW, Little JP, Cochran AJ, Hector AJ, Cashaback JG, Gibala MJ, Potvin JR, Baker SK, Phillips SM. Muscle time under tension during resistance exercise stimulates differential muscle protein sub-fractional synthetic responses in men. J Physiol. 2012 Jan 15;590(2):351-62. doi: 10.1113/jphysiol.2011.221200. Epub 2011 Nov 21.</citation>
      <PMID>22106173</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of Nottingham</investigator_affiliation>
      <investigator_full_name>Bethan Phillips</investigator_full_name>
      <investigator_title>Professor of Translational Physiology</investigator_title>
    </responsible_party>
    <keyword>Muscle</keyword>
    <keyword>Protein Synthesis</keyword>
    <keyword>Neuromuscular electrical stimulation</keyword>
    <keyword>Muscle blood flow</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Muscular Atrophy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05997095
  org study id: FMHS 261-0423
  nct id: NCT05997095
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Skeletal muscle accounts for approximately 45-55% of total body mass in healthy adults and
        plays a pivotal role in whole-body metabolic health, locomotion and physical independence.
        Undesirable loss of skeletal muscle mass (atrophy) is, however, a common feature of many
        communicable and non-communicable diseases including ageing, bed-rest/immobilisation, cancer
        and physical inactivity. As such, the design of optimal strategies (e.g., different types of
        exercise) to "offset" these detrimental losses of muscle is a focus for both researchers and
        clinicians.
  
        One situation where losses of muscle mass occur very quickly (i.e., within a few days) is
        after surgery. However, at this time, most people (especially if they have had major
        abdominal or lower-limb surgery) are not able to perform exercise and as such a different
        strategy to maintain muscle mass needs to be found. It has been shown that electrical
        stimulation of the leg muscles can maintain muscle mass and function in patients after
        surgery. It is not however yet known, what the optimal electrical stimulation regime is to
        preserve muscle mass during situations of disuse.
  
        This study aims to examine the impact of three different electrical stimulation protocols on
        muscle building processes in individuals age-matched to those most commonly presenting for
        major abdominal surgery. This information will then be used in a clinical trial of surgical
        patients to see if it can preserve their muscle mass and function in the post-operative
        period.
  The contraction of skeletal muscles depends on the regulation of the nervous system and the
        coordination of neuromuscular function. The smallest motor nervous system associated with
        muscle contraction is the motor unit (MU), which consists of an efferent motor neuron and all
        of the muscle fibres it innervates. Muscle tissue also undergoes adaptive alternations in
        response to external stimuli, such as the gradual decline in muscle mass and strength during
        ageing, and atrophy following muscle disuse. A number of studies have demonstrated that
        different types of voluntary movements, such as resistance exercise training (RET), can
        prevent or attenuate such alternations to a certain extent via increases in muscle protein
        synthesis (MPS).
  
        However, certain situations such as post-operative bed rest render RET interventions an
        unachievable option. Neuromuscular electrical stimulation (NMES) can be applied as a
        surrogate; acting to evoke involuntary contraction of the target muscles via electrical
        current applied to the muscle belly. Although NMES stimulation has been widely tested in the
        intensive care environment, results have shown variable efficacy- perhaps due to the
        multi-organ failure and associated catabolic systemic environment encountered by the majority
        of these patients.
  
        It has recently shown that in post-operative abdominal surgery patients, 5-days of NMES,
        performed at frequency of 30 Hz in a 1 second "on", 1 second "off" contraction pattern, can
        mitigate losses in muscle mass and function. However, this study 'borrowed' a protocol from
        previous intensive care literature, and as such may not be optimal with regards to frequency
        or contraction pattern. Given that this protocol was highly tolerated by patients in a
        previous study (i.e., based on 30 min of daily NMES, patients in this study said they would
        tolerate it for 45 to 240 (mean 90) min), it is plausible that higher frequency NMES (~100
        Hz), enabling greater force production may be both viable and result in further mitigation of
        muscle mass and function losses. It has also been demonstrated that the time muscle is under
        loaded tension during RET may be an important modulator of MPS and subsequent gains in muscle
        mass. Therefore, increasing the contraction relative to relaxation time during NMES (e.g., 3
        seconds on, 1 second off) may be another feasible and perhaps more beneficial strategy to
        reduce muscle mass losses in populations where an increase in frequency may not be possible
        or tolerable.
  
        Knowing that muscle maintenance is based on a dynamic equilibrium between MPS and muscle
        protein breakdown, the impact of different NMES protocols on MPS, associated cell signalling,
        and nutrient delivery pathways needs to be explored so that an optimal intervention can be
        tested in clinical settings associated with disuse atrophy. To date, no previous studies have
        compared differing frequencies of NMES on the muscle metabolic responses in older adults, nor
        the effect of differing NMES-induced contraction patterns.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Skeletal Muscle Protein Synthesis
  time frame: 4 hours
  description: A primed continuous infusion of a stable isotope tracer (1,2 13C2] leucine) will be initiated (Prime: 0.7 mg/kg; Constant: 1.0 mg/kg/h) at time 0h. After 60 min of stable isotope infusion, a single muscle biopsy will be taken from one leg. Another biopsy from the same leg will be taken 120 min later, and a third 240 min after the second to provide rates of muscle protein synthesis in the rested condition and in response to NMES, respectively. The fractional synthetic rate (FSR) of the myofibrillar fraction was calculated from the incorporation of [1,2 13C2] leucine, using venous plasma labelling between muscle biopsies to represent the immediate precursor for protein synthesis. This will give a rate (%/hour) of muscle protein synthesis.
  measure: Skeletal Muscle Anabolic Signalling
  time frame: 4 hours
  description: Total and phosphorylation of established anabolic proteins in human skeletal muscle will be quantified via Western Blotting.
  measure: Skeletal Muscle Blood Flow
  time frame: Baseline and 30 minutes post neuromuscular stimulation
  description: Contrast enhanced ultrasound (CEUS) measurements will be made 60 min before the NMES and 30 min after. To achieve this, a custom-made probe holder will be placed on the leg to be stimulated at the start of the study. For each measurement, Sonovue will be infused at 2ml/min for 1 minute and then 1ml/min for 30 sec to achieve systemic steady state, with a continued infusion at 1ml/min for the duration of the measurements. Each measurement will include three, 30-second capture-flash cycles which will form a Sonovue replenishment curve for the portion of vastus lateralis muscle (VL) under the probe. blood flow will be calculated by measuring the reperfusion rate of the microbubbles in the muscle microvasculature following destruction with a high mechanical index flash, given the infusion of contrast is continuous.
  measure: Perceived discomfort of Neuromuscular Electrical stimulation
  time frame: Immediately post neuromuscular stimulation
  description: At the end of the NMES, participants will be asked to rate the perceived discomfort on a Likert scale of 1-10 and respond to the question of "that stimulation was 30-minutes, how much longer would you have been willing to have stimulation for if you were in bed recovering from an injury or illness i.e., it was not interfering with your ability to perform other activities?"
  arm group label: 30Hz (low-intensity)
  arm group type: Active Comparator
  description: Volunteers receive 30 mins of neuromuscular electrical stimulation at 30Hz with a contraction pattern of 1 second "on" and 1 second "off"
  arm group label: 100Hz (higher-intensity)
  arm group type: Experimental
  description: Volunteers receive 30 mins of neuromuscular electrical stimulation at 100Hz with a contraction pattern of 1 second "on" and 1 second "off"
  arm group label: 30Hz (low-intensity, 3:1)
  arm group type: Experimental
  description: Volunteers receive 30 mins of neuromuscular electrical stimulation at 30Hz with a contraction pattern of 3 seconds "on" and 1 second "off"
  intervention type: Other
  intervention name: Neuromuscular electrical stimulation (NMES/0
  description: NMES will be applied for 30 min and will be delivered using an approved, CE-marked device (Premier Combo Plus, Med-Fit Ltd, UK) using two large (7.5 × 13 cm) electrodes placed proximally and distally over the lateral quadriceps. The set protocols will be pre-programmed into to the device and the amplitude value will match the setting that was determined during a familiarisation visit
  arm group label: 100Hz (higher-intensity)
  arm group label: 30Hz (low-intensity)
  arm group label: 30Hz (low-intensity, 3:1)
  criteria: 
  gender: All
  minimum age: 60 Years
  maximum age: 85 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Bethan Phillips, PhD
  phone: 01332 724676
  email: beth.phillips@nottingham.ac.uk
  last name: Mathew Piasecki, PhD
  phone: 01332 724688
  email: Mathew.Piasecki@nottingham.ac.uk
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United Kingdom
  citation: Hardy EJ, Hatt J, Doleman B, Smart TF, Piasecki M, Lund JN, Phillips BE. Post-operative electrical muscle stimulation attenuates loss of muscle mass and function following major abdominal surgery in older adults: a split body randomised control trial. Age Ageing. 2022 Oct 6;51(10):afac234. doi: 10.1093/ageing/afac234.
  PMID: 36315433
  citation: Hardy EJO, Inns TB, Hatt J, Doleman B, Bass JJ, Atherton PJ, Lund JN, Phillips BE. The time course of disuse muscle atrophy of the lower limb in health and disease. J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2616-2629. doi: 10.1002/jcsm.13067. Epub 2022 Sep 14.
  PMID: 36104842
  citation: Wall BT, Dirks ML, Verdijk LB, Snijders T, Hansen D, Vranckx P, Burd NA, Dendale P, van Loon LJ. Neuromuscular electrical stimulation increases muscle protein synthesis in elderly type 2 diabetic men. Am J Physiol Endocrinol Metab. 2012 Sep 1;303(5):E614-23. doi: 10.1152/ajpendo.00138.2012. Epub 2012 Jun 26.
  PMID: 22739107
  citation: Mancinelli R, Toniolo L, Di Filippo ES, Doria C, Marrone M, Maroni CR, Verratti V, Bondi D, Maccatrozzo L, Pietrangelo T, Fulle S. Neuromuscular Electrical Stimulation Induces Skeletal Muscle Fiber Remodeling and Specific Gene Expression Profile in Healthy Elderly. Front Physiol. 2019 Nov 27;10:1459. doi: 10.3389/fphys.2019.01459. eCollection 2019.
  PMID: 31827446
  citation: Burd NA, Andrews RJ, West DW, Little JP, Cochran AJ, Hector AJ, Cashaback JG, Gibala MJ, Potvin JR, Baker SK, Phillips SM. Muscle time under tension during resistance exercise stimulates differential muscle protein sub-fractional synthetic responses in men. J Physiol. 2012 Jan 15;590(2):351-62. doi: 10.1113/jphysiol.2011.221200. Epub 2011 Nov 21.
  PMID: 22106173
  responsible party type: Principal Investigator
  investigator affiliation: University of Nottingham
  investigator full name: Bethan Phillips
  investigator title: Professor of Translational Physiology
  mesh term: Muscular Atrophy
  sharing ipd: No