<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/NCT02247895</url>
  </required_header>
  <id_info>
    <org_study_id>062014</org_study_id>
    <secondary_id>14-0237-F3R</secondary_id>
    <nct_id>NCT02247895</nct_id>
  </id_info>
  <brief_title>Treatment of Muscle Weakness in Critically Ill Patients</brief_title>
  <official_title>Effect of Treatment With the Niveus Medical Muscle Stimulation System 110 on Quadriceps Strength In Mechanically Ventilated Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gerald Supinski</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients who are admitted to the intensive care unit and require mechanical ventilation&#xD;
      frequently develop profound respiratory and limb muscle weakness. Studies show that the&#xD;
      development of weakness during the ICU stay results in poor outcomes. Currently there are no&#xD;
      treatments for this muscle weakness, but it has been suggested that this weakness might&#xD;
      improve with physical therapy. Electrical stimulation is a method to provide direct&#xD;
      stimulation to the muscles potentially enhancing function and improving strength. The purpose&#xD;
      of this study is to test the hypothesis that neuromuscular electrical stimulation of the&#xD;
      quadriceps muscle will improve muscle strength in patients who are critically ill on&#xD;
      mechanical ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The basic study design is to:&#xD;
&#xD;
        1. Obtain informed consent from patient or the patients LAR&#xD;
&#xD;
        2. Randomize subjects to treatment with either:&#xD;
&#xD;
             1. Sham therapy, consisting of bilateral placement of Niveus Medical Muscle&#xD;
                Stimulation System 110 electrodes for 30 minutes twice daily without activation of&#xD;
                the electrical circuitry of the unit, or&#xD;
&#xD;
             2. Active therapy, using the Niveus Medical Muscle Stimulation System 110 electrodes&#xD;
                to actively produce a rhythmic quadriceps contraction for 30 minutes twice daily&#xD;
&#xD;
        3. Measure magnetic stimulated quadriceps twitch (QuadTw) strength bilaterally as well as&#xD;
           ultrasound assessment of quadriceps size&#xD;
&#xD;
        4. Continue sham or active treatment daily for 7 days for a total of 14 sessions&#xD;
&#xD;
        5. Repeat measurements of magnetic stimulated QuadTw strength and ultrasound assessment of&#xD;
           quadriceps size on Day 8 or before Day 8 if the subject is to be discharged from the&#xD;
           hospital prior to the allotted duration of sham or active treatment&#xD;
&#xD;
        6. Functional measurement of the patient using the Functional Status Score for the ICU&#xD;
           (FSS-ICU) at the end of the treatment period or upon discharge&#xD;
&#xD;
        7. A member of the research team will visit the subject until hospital discharge and will&#xD;
           record total duration (days) of mechanical ventilation, duration (days) of mechanical&#xD;
           ventilation following study entry, duration of ICU stay, ventilator weaning time (days&#xD;
           measured from time of first spontaneous breathing trial to extubation), and total&#xD;
           duration (days) of hospitalization&#xD;
&#xD;
        8. The investigators will also review each subject's medical record on entry into the study&#xD;
           to obtain demographic information including the following: age, sex, diagnoses,&#xD;
           medications, reason for institution of mechanical ventilation, vital signs at the time&#xD;
           of the initial visit, bedside parameters of mechanical ventilation use (including mode&#xD;
           of ventilation, duration of ventilation, level of oxygen, breath volume and rate, %&#xD;
           triggered breaths), most recent arterial blood gas values, and chest radiograph readings&#xD;
           at the time of the initial visit. The investigators will also record the subject's&#xD;
           weight, BMI and total intake and output values since admission to the ICU. In addition,&#xD;
           investigators will monitor each subject's progress in the ICU daily by reviewing the&#xD;
           subject's medical record and recording the clinical parameters as well as recording&#xD;
           daily weights and total intake and output. These parameters will also be assessed until&#xD;
           the time that the patient is discharged from the ICU. In addition, the investigators&#xD;
           will record and note all physical therapy and occupational therapy sessions that the&#xD;
           subject receives as part of the standard of care in the ICU and in the hospital up until&#xD;
           the time of discharge. In the University of Kentucky hospital, occupational therapy&#xD;
           records the Barthel Index at each session which uses a scale of 0-100 to assess an&#xD;
           individual's functional independence when performing activities of daily living (ADLs).&#xD;
           Physical therapy assesses functional status using Kansas University Hospital Physical&#xD;
           Therapy Acute Care Functional Outcomes, which also assesses functional status in the&#xD;
           categories of bed mobility, transfer, gait and walking distance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    difficulty meeting enrollment goals&#xD;
  </why_stopped>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">February 2018</completion_date>
  <primary_completion_date type="Actual">February 2018</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>Device Feasibility</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Technical Feasibility, that is ability to complete therapy sessions</measure>
    <time_frame>Discharge from ICU, Average 7-10 days</time_frame>
    <description>Percentage of patients who completed treatment with the device</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total ICU length of stay</measure>
    <time_frame>Discharge from ICU, Average 7-10 days</time_frame>
    <description>Average 7-10 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Length of Stay</measure>
    <time_frame>Hospital discharge, Average 14-21 days</time_frame>
    <description>Average 14-21 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional Status Score for ICU</measure>
    <time_frame>ICU discharge, Average 7-10 days after study entry</time_frame>
    <description>Average 7-10 days after study entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation after study entry</measure>
    <time_frame>Until patient is successfully weaned from mechanical ventilation, Average 4-10 days</time_frame>
    <description>Average 4-10 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quadriceps twitch force generation</measure>
    <time_frame>Baseline (prior to Treatment) and Day 8</time_frame>
    <description>Quadriceps twitch force generation will be measured using magnetic stimulation of each femoral nerve and compared to measurements obtained at the time of study entry (baseline-prior to randomization)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Rectus Femorus thickness</measure>
    <time_frame>Day 8</time_frame>
    <description>Rectus femorus thickness will be measured using ultrasound at baseline (study entry) and on Day 8 of study after either sham treatment or neuromuscular stimulation</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Critical Illness</condition>
  <condition>Respiratory Failure</condition>
  <condition>Myopathy</condition>
  <condition>Weakness</condition>
  <arm_group>
    <arm_group_label>Sham Treatment</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham stimulation twice daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The active treatment group will receive neuromuscular electrical stimulation to both quadriceps muscle for 30 minutes twice daily for a total of 14 treatments.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Treatment</intervention_name>
    <description>Subjects will undergo the same protocol as the treatment group except no electrical stimulation will be applied.</description>
    <arm_group_label>Sham Treatment</arm_group_label>
    <other_name>Sham treatment without electrical stimulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Electrical stimulation</intervention_name>
    <description>Two thirty minute sessions of neuromuscular electrical stimulation applied to both quadriceps for seven days for a total of 14 treatments</description>
    <arm_group_label>Active Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Acute respiratory failure requiring mechanical ventilation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Attending physician on service determines that patient too unstable to tolerate&#xD;
             measurements&#xD;
&#xD;
          -  Patient requires &gt; 15mcg/min norepinephrine or &gt; 15mg/kg/min of dopamine.&#xD;
&#xD;
          -  Fraction of inspired oxygen &gt; 80% or positive end expiratory pressure &gt; 15 cm H20&#xD;
             requirements.&#xD;
&#xD;
          -  Cardiac pacemaker or implanted defibrillator.&#xD;
&#xD;
          -  Neuromuscular blocking agents delivered within 48 hours of preceding testing.&#xD;
&#xD;
          -  Existing neuromuscular disease.&#xD;
&#xD;
          -  Profound uncorrectable hypokalemia (&lt; 2.5) OR hypophosphatemia (&lt; 1.0)&#xD;
&#xD;
          -  Acute lower extremity deep vein thrombosis&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Prisoner&#xD;
&#xD;
          -  Institutionalized patient&#xD;
&#xD;
          -  If primary attending determines that patient is terminal and will likely have care&#xD;
             withdrawn within 7 days&#xD;
&#xD;
          -  Do not resuscitate order&#xD;
&#xD;
          -  Body mass index &gt; 40&#xD;
&#xD;
          -  Patients requiring mechanical ventilation more than 4 days prior to study entry&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gerald S. Supinski, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky Medical Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40586</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>June 18, 2020</last_update_submitted>
  <last_update_submitted_qc>June 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Gerald Supinski</investigator_full_name>
    <investigator_title>Staff Physician, Division of Pulmonary, Critical Care and Sleep Medicine, Principal Investigator, Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>ICU Acquired weakness</keyword>
  <keyword>Critical illness</keyword>
  <keyword>Mechanical ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
    <mesh_term>Asthenia</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/NCT02247895
org study id: 062014
secondary id: 14-0237-F3R
nct id: NCT02247895
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
Patients who are admitted to the intensive care unit and require mechanical ventilation
      frequently develop profound respiratory and limb muscle weakness. Studies show that the
      development of weakness during the ICU stay results in poor outcomes. Currently there are no
      treatments for this muscle weakness, but it has been suggested that this weakness might
      improve with physical therapy. Electrical stimulation is a method to provide direct
      stimulation to the muscles potentially enhancing function and improving strength. The purpose
      of this study is to test the hypothesis that neuromuscular electrical stimulation of the
      quadriceps muscle will improve muscle strength in patients who are critically ill on
      mechanical ventilation.
The basic study design is to:

        1. Obtain informed consent from patient or the patients LAR

        2. Randomize subjects to treatment with either:

             1. Sham therapy, consisting of bilateral placement of Niveus Medical Muscle
                Stimulation System 110 electrodes for 30 minutes twice daily without activation of
                the electrical circuitry of the unit, or

             2. Active therapy, using the Niveus Medical Muscle Stimulation System 110 electrodes
                to actively produce a rhythmic quadriceps contraction for 30 minutes twice daily

        3. Measure magnetic stimulated quadriceps twitch (QuadTw) strength bilaterally as well as
           ultrasound assessment of quadriceps size

        4. Continue sham or active treatment daily for 7 days for a total of 14 sessions

        5. Repeat measurements of magnetic stimulated QuadTw strength and ultrasound assessment of
           quadriceps size on Day 8 or before Day 8 if the subject is to be discharged from the
           hospital prior to the allotted duration of sham or active treatment

        6. Functional measurement of the patient using the Functional Status Score for the ICU
           (FSS-ICU) at the end of the treatment period or upon discharge

        7. A member of the research team will visit the subject until hospital discharge and will
           record total duration (days) of mechanical ventilation, duration (days) of mechanical
           ventilation following study entry, duration of ICU stay, ventilator weaning time (days
           measured from time of first spontaneous breathing trial to extubation), and total
           duration (days) of hospitalization

        8. The investigators will also review each subject's medical record on entry into the study
           to obtain demographic information including the following: age, sex, diagnoses,
           medications, reason for institution of mechanical ventilation, vital signs at the time
           of the initial visit, bedside parameters of mechanical ventilation use (including mode
           of ventilation, duration of ventilation, level of oxygen, breath volume and rate, %
           triggered breaths), most recent arterial blood gas values, and chest radiograph readings
           at the time of the initial visit. The investigators will also record the subject's
           weight, BMI and total intake and output values since admission to the ICU. In addition,
           investigators will monitor each subject's progress in the ICU daily by reviewing the
           subject's medical record and recording the clinical parameters as well as recording
           daily weights and total intake and output. These parameters will also be assessed until
           the time that the patient is discharged from the ICU. In addition, the investigators
           will record and note all physical therapy and occupational therapy sessions that the
           subject receives as part of the standard of care in the ICU and in the hospital up until
           the time of discharge. In the University of Kentucky hospital, occupational therapy
           records the Barthel Index at each session which uses a scale of 0-100 to assess an
           individual's functional independence when performing activities of daily living (ADLs).
           Physical therapy assesses functional status using Kansas University Hospital Physical
           Therapy Acute Care Functional Outcomes, which also assesses functional status in the
           categories of bed mobility, transfer, gait and walking distance.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Device Feasibility
masking: Single (Investigator)
measure: Technical Feasibility, that is ability to complete therapy sessions
time frame: Discharge from ICU, Average 7-10 days
description: Percentage of patients who completed treatment with the device
measure: Total ICU length of stay
time frame: Discharge from ICU, Average 7-10 days
description: Average 7-10 days
measure: Hospital Length of Stay
time frame: Hospital discharge, Average 14-21 days
description: Average 14-21 days
measure: Functional Status Score for ICU
time frame: ICU discharge, Average 7-10 days after study entry
description: Average 7-10 days after study entry
measure: Duration of mechanical ventilation after study entry
time frame: Until patient is successfully weaned from mechanical ventilation, Average 4-10 days
description: Average 4-10 days
measure: Change in quadriceps twitch force generation
time frame: Baseline (prior to Treatment) and Day 8
description: Quadriceps twitch force generation will be measured using magnetic stimulation of each femoral nerve and compared to measurements obtained at the time of study entry (baseline-prior to randomization)
measure: Rectus Femorus thickness
time frame: Day 8
description: Rectus femorus thickness will be measured using ultrasound at baseline (study entry) and on Day 8 of study after either sham treatment or neuromuscular stimulation
arm group label: Sham Treatment
arm group type: Sham Comparator
description: Sham stimulation twice daily
arm group label: Active Treatment
arm group type: Active Comparator
description: The active treatment group will receive neuromuscular electrical stimulation to both quadriceps muscle for 30 minutes twice daily for a total of 14 treatments.
intervention type: Device
intervention name: Sham Treatment
description: Subjects will undergo the same protocol as the treatment group except no electrical stimulation will be applied.
arm group label: Sham Treatment
other name: Sham treatment without electrical stimulation
intervention type: Device
intervention name: Electrical stimulation
description: Two thirty minute sessions of neuromuscular electrical stimulation applied to both quadriceps for seven days for a total of 14 treatments
arm group label: Active Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Gerald S. Supinski, MD
role: Principal Investigator
affiliation: Professor of Medicine
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Gerald Supinski
investigator title: Staff Physician, Division of Pulmonary, Critical Care and Sleep Medicine, Principal Investigator, Professor of Medicine
mesh term: Respiratory Insufficiency
mesh term: Critical Illness
mesh term: Asthenia