<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/NCT04468191</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY20060082</org_study_id>
    <nct_id>NCT04468191</nct_id>
  </id_info>
  <brief_title>Fatigue in Patients With Amyotrophic Lateral Sclerosis</brief_title>
  <official_title>Quantifying Fatigue of the Respiratory and Swallowing Musculature in Patients With Amyotrophic Lateral Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cara Donohue</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</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>
      Expiratory muscle strength training (EMST) is an emerging palliative intervention for&#xD;
      prolonging pulmonary and swallow function in patients with amyotrophic lateral sclerosis&#xD;
      (PALS), but it is unknown whether EMST may result in detrimental immediate to short-term&#xD;
      fatigue because there is no way to measure fatigue non-invasively. This study will determine&#xD;
      the immediate to short-term impact of EMST on objective respiratory and swallow function,&#xD;
      whether subjective ratings of dyspnea and fatigue map to objective decompensation of&#xD;
      respiratory and swallow function, and the ability to monitor fatigue of the respiratory and&#xD;
      swallowing musculature non-invasively. Findings from this research study will provide&#xD;
      preliminary evidence regarding optimal timing for PALS to complete EMST and will provide PALS&#xD;
      and clinicians increased capabilities to monitor fatigue non-invasively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research proposal will determine the immediate impact of expiratory muscle strength&#xD;
      training (EMST) on fatigue of the respiratory and swallowing musculature, whether objective&#xD;
      decompensation translates to subjective dyspnea and fatigue, and whether high resolution&#xD;
      cervical auscultation (HRCA) signal features can noninvasively capture and characterize&#xD;
      physiologic decompensation that relates to fatigue in patients with amyotrophic lateral&#xD;
      sclerosis (PALS) via three Specific Aims.&#xD;
&#xD;
      Aim 1) Determine the impact of one EMST session on objective respiratory and swallow&#xD;
      function.&#xD;
&#xD;
      Hypothesis 1) One EMST session will result in reduced pulmonary function tests (PFTs)&#xD;
      (maximum expiratory pressure, forced vital capacity, peak cough flow) and declines in swallow&#xD;
      function (Videofluoroscopy (VF), HRCA). PALS will have greater reductions in PFTs, and&#xD;
      objective declines in swallow function after the experimental condition compared to the&#xD;
      control condition.&#xD;
&#xD;
      Aim 2) Determine if objective decompensation translates to subjective ratings of dyspnea and&#xD;
      fatigue after one EMST session.&#xD;
&#xD;
      Hypothesis 2) Subjective ratings of dyspnea and fatigue (Situational Fatigue Scale; Dyspnea&#xD;
      ALS-15) will be associated with objective decompensation in respiratory and swallow function&#xD;
      (PFTs, VF, HRCA) after one EMST session.&#xD;
&#xD;
      Aim 3) Investigate whether HRCA signal features analyses can non-invasively characterize&#xD;
      immediate post-exercise physiologic changes in swallowing function that are related to&#xD;
      fatigue.&#xD;
&#xD;
      Hypothesis 3) Pre- to post-EMST changes in HRCA signal features will be associated with&#xD;
      physiologic changes in swallowing as measured by VF analyses.&#xD;
&#xD;
      This study will be a prospective study with randomized experimental and control conditions;&#xD;
      and is directly related to the NIH funded research studies currently conducted in the&#xD;
      Computational Deglutition (CD) Lab under the leadership of Dr. James Coyle and Dr. Ervin&#xD;
      Sejdic.&#xD;
&#xD;
      Participants: 20 PALS will be recruited to undergo VF before and after undergoing the&#xD;
      randomly ordered experimental and control conditions on two separate nonconsecutive days&#xD;
      within a two-week time frame.&#xD;
&#xD;
      Baseline Procedures:&#xD;
&#xD;
      PALS will be instructed not to eat a meal or engage in exercise within two hours of their&#xD;
      visit. Following consent, baseline assessment procedures be obtained. All baseline&#xD;
      measurements of swallowing and pulmonary function will be performed before any potentially&#xD;
      fatigue-inducing procedures are performed (i.e. exercise training).&#xD;
&#xD;
        1. The ALS functional rating scale revised (ALSFRS-R) (an instrument used to assess changes&#xD;
           in functional status over time in PALS), will be completed.&#xD;
&#xD;
        2. Prior to completing swallowing and pulmonary measurements, PALS will complete the&#xD;
           situational fatigue scale (SFS), which measures fatigue that results from completing&#xD;
           functional daily activities.&#xD;
&#xD;
        3. Before undergoing swallowing and pulmonary measurements, PALS will also complete the&#xD;
           Dyspnea ALS-15 (DALS-15), which is a measure of dyspnea that is known to be related to&#xD;
           fatigue in PALS.&#xD;
&#xD;
        4. PALS will undergo an assessment of swallow function with concurrent recordings of&#xD;
           videofluoroscopy (VF) and high-resolution cervical auscultation (HRCA) signals prior to&#xD;
           undergoing PFTs to mitigate fatigue from the PFTs as a confound. VF procedures will be&#xD;
           conducted first, because ten swallows of thin liquid are unlikely to cause fatigue of&#xD;
           the respiratory and swallow musculature that would impact PFTs.&#xD;
&#xD;
        5. PALS will be seated upright in a chair and viewed in the lateral plane. HRCA signals&#xD;
           will be simultaneously recorded from neck sensors (a contact microphone and&#xD;
           accelerometer) that are attached to the anterior laryngeal framework with tape. VF and&#xD;
           HRCA signals will be recorded onto a Labview Workstation. During each stage (pre-, post&#xD;
           EMST) of VF, PALS will swallow ten thin liquid boluses of barium. Five liquid swallows&#xD;
           will be a self-selected comfortable sip from a cup and five will be 3mL by spoon&#xD;
           administered with a command to swallow. Presentation order for the liquid swallows will&#xD;
           be randomized using a random number generator. If more than one aspiration event is&#xD;
           observed during VF, the exam will be terminated immediately in order to ensure patient&#xD;
           safety.&#xD;
&#xD;
        6. PFTs following VF will include maximum expiratory pressure (MEP) (measured with the&#xD;
           MicroRPM handheld MEP device (Micro Direct Inc., Lewiston, ME)), peak cough flow (PCF)&#xD;
           (measured with a handheld peak flow meter (BV Medical, Barrington, IL)), and FVC&#xD;
           (measured with the Spirodoc spirometer and WinspiroPRO computer software (Medical&#xD;
           International Research, New Berlin, WI)). All PFTs will be completed three times with&#xD;
           PALS sitting in an upright seated position with a nose clip in line with standard PFT&#xD;
           protocols. The highest of three measurements will be used for analyses.&#xD;
&#xD;
      EMST Training: PALS will use the EMST-150 device (Aspire Products, Gainesville, Florida) or&#xD;
      the Philips Threshold PEP trainer (Philips Respironics, Cedar Grove, New Jersey). During the&#xD;
      experimental condition, EMST devices will be set to 50% of PALS' highest MEP from their&#xD;
      baseline PFT assessment. During the control condition, no resistance will be added, and the&#xD;
      loaded spring will be removed from the device. For both experimental conditions, PALS will&#xD;
      undergo the following standard treatment protocol:&#xD;
&#xD;
        1. PALS will complete five sets of five repetitions using an EMST device.&#xD;
&#xD;
        2. For each repetition, PALS will be instructed to take a deep breath in and blow until the&#xD;
           valve releases.&#xD;
&#xD;
        3. Between repetitions, PALs will have 10-15 seconds of rest before the next repetition.&#xD;
&#xD;
        4. After each set, PALS will rest for one minute before completing the next set.&#xD;
&#xD;
      Post-treatment procedures: Following the EMST session with either the device set to 50% load&#xD;
      or the sham device, PALS will undergo the same procedures (VF, HRCA, PFTs) as described above&#xD;
      in steps 1-6 of the baseline procedures&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    COVID-19 pandemic restrictions for data collection&#xD;
  </why_stopped>
  <start_date type="Actual">February 10, 2021</start_date>
  <completion_date type="Actual">February 10, 2021</completion_date>
  <primary_completion_date type="Actual">February 10, 2021</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>
    <intervention_model_description>This study will be a prospective study with randomized experimental and control conditions. Patients with ALS will undergo the experimental and control conditions in random order on two separate days within a two-week time frame.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
    <masking_description>During the experimental condition, expiratory muscle strength training (EMST) devices will be set to 50% of patients with ALS' highest maximum expiratory pressure from their baseline pulmonary function test assessment. During the control condition, no resistance will be added, and the loaded spring will be removed from the device. For both experimental conditions, patients with ALS will be blinded to condition.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in forced vital capacity (FVC) between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in forced vital capacity (FVC) between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in peak cough flow (PCF) between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>PCF is a measure of air flow during a cough.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in peak cough flow (PCF) between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>PCF is a measure of air flow during a cough.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in maximum expiratory pressure (MEP) between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in maximum expiratory pressure (MEP) between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in temporal kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in temporal kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in spatial kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in spatial kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Modified Barium Swallow Impairment Profile (MBSImP) scores of swallowing between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Modified Barium Swallow Impairment Profile (MBSImP) scores of swallowing between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in high resolution cervical auscultation (HRCA) signal features between pre and post expiratory muscle strength training (EMST) experimental session</measure>
    <time_frame>pre and post EMST experimental session, up to 2 weeks</time_frame>
    <description>Feature extraction and analyses from HRCA will be completed before and after each EMST session and compared to VF to determine whether HRCA can detect fatigue related changes in swallow function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in high resolution cervical auscultation (HRCA) signal features between pre and post expiratory muscle strength training (EMST) sham session</measure>
    <time_frame>pre and post EMST sham session, up to 2 weeks</time_frame>
    <description>Feature extraction and analyses from HRCA will be completed before and after each EMST session and compared to VF to determine whether HRCA can detect fatigue related changes in swallow function.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <condition>Dysphagia</condition>
  <condition>Dyspnea</condition>
  <condition>Respiration Disorders</condition>
  <arm_group>
    <arm_group_label>Experimental, then sham</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with ALS in the experimental, then sham arm will undergo an expiratory muscle strength training (EMST) session with a device set to 50% of patients with ALS' highest maximum expiratory pressure from their baseline pulmonary function test assessment during their first study visit. Then, during their second study visit, patients with ALS will undergo an EMST session with a device set to 0% resistance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham, then experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with ALS in the sham, then experimental arm will undergo an expiratory muscle strength training (EMST) session with a device set to 0% resistance during their first study visit. Then, during their second study visit, patients with ALS will undergo an EMST session with a device set to 50% of patients with ALS' highest maximum expiratory pressure from their baseline pulmonary function test assessment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Experimental expiratory muscle strength training (EMST)</intervention_name>
    <description>The experimental EMST will involve blowing into a device with a spring-loaded valve set to 50% of the patient with ALS' maximum expiratory pressure.</description>
    <arm_group_label>Experimental, then sham</arm_group_label>
    <arm_group_label>Sham, then experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham expiratory muscle strength training (EMST)</intervention_name>
    <description>The sham EMST will involve blowing into a device without a spring-loaded valve (0% resistance).</description>
    <arm_group_label>Experimental, then sham</arm_group_label>
    <arm_group_label>Sham, then experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of ALS defined as possible, probable, or definite by a neurologist using the&#xD;
             El Escorial criteria&#xD;
&#xD;
          -  FVC&gt;65% predicted&#xD;
&#xD;
          -  adequate cognition as defined by a score of &gt;10 on the ALS Cognitive Behavioral Screen&#xD;
&#xD;
          -  adequate labial seal for completing pulmonary function tests and expiratory muscle&#xD;
             strength training (EMST)&#xD;
&#xD;
          -  on a regular/thin liquid diet&#xD;
&#xD;
          -  no allergies to barium&#xD;
&#xD;
          -  not oxygen-dependent&#xD;
&#xD;
          -  no tracheostomy/ mechanical ventilation&#xD;
&#xD;
          -  no history of other neurological or respiratory disorders&#xD;
&#xD;
          -  no history of smoking&#xD;
&#xD;
          -  no history of head and neck cancer or other major head/neck surgery or radiation&#xD;
             therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  FVC&lt;65% predicted&#xD;
&#xD;
          -  inadequate cognition as defined by a score of &lt;10 on the ALS Cognitive Behavioral&#xD;
             Screen -inadequate labial seal for completing pulmonary function tests and expiratory&#xD;
             muscle strength training (EMST)&#xD;
&#xD;
          -  not on a regular/thin liquid diet&#xD;
&#xD;
          -  allergies to barium&#xD;
&#xD;
          -  oxygen-dependent&#xD;
&#xD;
          -  presence of tracheostomy/dependent on mechanical ventilation&#xD;
&#xD;
          -  history of other neurological or respiratory disorders&#xD;
&#xD;
          -  history of smoking&#xD;
&#xD;
          -  history of head and neck cancer or other major head/neck surgery or radiation therapy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cara A Donohue, MA CCC-SLP</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>James L Coyle, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center Presbyterian Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15260</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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  <verification_date>February 2021</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>February 10, 2021</last_update_submitted>
  <last_update_submitted_qc>February 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Cara Donohue</investigator_full_name>
    <investigator_title>MA CCC-SLP/PhD Student</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyspnea</mesh_term>
    <mesh_term>Respiration Disorders</mesh_term>
    <mesh_term>Motor Neuron Disease</mesh_term>
    <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <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/NCT04468191
org study id: STUDY20060082
nct id: NCT04468191
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
Expiratory muscle strength training (EMST) is an emerging palliative intervention for
      prolonging pulmonary and swallow function in patients with amyotrophic lateral sclerosis
      (PALS), but it is unknown whether EMST may result in detrimental immediate to short-term
      fatigue because there is no way to measure fatigue non-invasively. This study will determine
      the immediate to short-term impact of EMST on objective respiratory and swallow function,
      whether subjective ratings of dyspnea and fatigue map to objective decompensation of
      respiratory and swallow function, and the ability to monitor fatigue of the respiratory and
      swallowing musculature non-invasively. Findings from this research study will provide
      preliminary evidence regarding optimal timing for PALS to complete EMST and will provide PALS
      and clinicians increased capabilities to monitor fatigue non-invasively.
This research proposal will determine the immediate impact of expiratory muscle strength
      training (EMST) on fatigue of the respiratory and swallowing musculature, whether objective
      decompensation translates to subjective dyspnea and fatigue, and whether high resolution
      cervical auscultation (HRCA) signal features can noninvasively capture and characterize
      physiologic decompensation that relates to fatigue in patients with amyotrophic lateral
      sclerosis (PALS) via three Specific Aims.

      Aim 1) Determine the impact of one EMST session on objective respiratory and swallow
      function.

      Hypothesis 1) One EMST session will result in reduced pulmonary function tests (PFTs)
      (maximum expiratory pressure, forced vital capacity, peak cough flow) and declines in swallow
      function (Videofluoroscopy (VF), HRCA). PALS will have greater reductions in PFTs, and
      objective declines in swallow function after the experimental condition compared to the
      control condition.

      Aim 2) Determine if objective decompensation translates to subjective ratings of dyspnea and
      fatigue after one EMST session.

      Hypothesis 2) Subjective ratings of dyspnea and fatigue (Situational Fatigue Scale; Dyspnea
      ALS-15) will be associated with objective decompensation in respiratory and swallow function
      (PFTs, VF, HRCA) after one EMST session.

      Aim 3) Investigate whether HRCA signal features analyses can non-invasively characterize
      immediate post-exercise physiologic changes in swallowing function that are related to
      fatigue.

      Hypothesis 3) Pre- to post-EMST changes in HRCA signal features will be associated with
      physiologic changes in swallowing as measured by VF analyses.

      This study will be a prospective study with randomized experimental and control conditions;
      and is directly related to the NIH funded research studies currently conducted in the
      Computational Deglutition (CD) Lab under the leadership of Dr. James Coyle and Dr. Ervin
      Sejdic.

      Participants: 20 PALS will be recruited to undergo VF before and after undergoing the
      randomly ordered experimental and control conditions on two separate nonconsecutive days
      within a two-week time frame.

      Baseline Procedures:

      PALS will be instructed not to eat a meal or engage in exercise within two hours of their
      visit. Following consent, baseline assessment procedures be obtained. All baseline
      measurements of swallowing and pulmonary function will be performed before any potentially
      fatigue-inducing procedures are performed (i.e. exercise training).

        1. The ALS functional rating scale revised (ALSFRS-R) (an instrument used to assess changes
           in functional status over time in PALS), will be completed.

        2. Prior to completing swallowing and pulmonary measurements, PALS will complete the
           situational fatigue scale (SFS), which measures fatigue that results from completing
           functional daily activities.

        3. Before undergoing swallowing and pulmonary measurements, PALS will also complete the
           Dyspnea ALS-15 (DALS-15), which is a measure of dyspnea that is known to be related to
           fatigue in PALS.

        4. PALS will undergo an assessment of swallow function with concurrent recordings of
           videofluoroscopy (VF) and high-resolution cervical auscultation (HRCA) signals prior to
           undergoing PFTs to mitigate fatigue from the PFTs as a confound. VF procedures will be
           conducted first, because ten swallows of thin liquid are unlikely to cause fatigue of
           the respiratory and swallow musculature that would impact PFTs.

        5. PALS will be seated upright in a chair and viewed in the lateral plane. HRCA signals
           will be simultaneously recorded from neck sensors (a contact microphone and
           accelerometer) that are attached to the anterior laryngeal framework with tape. VF and
           HRCA signals will be recorded onto a Labview Workstation. During each stage (pre-, post
           EMST) of VF, PALS will swallow ten thin liquid boluses of barium. Five liquid swallows
           will be a self-selected comfortable sip from a cup and five will be 3mL by spoon
           administered with a command to swallow. Presentation order for the liquid swallows will
           be randomized using a random number generator. If more than one aspiration event is
           observed during VF, the exam will be terminated immediately in order to ensure patient
           safety.

        6. PFTs following VF will include maximum expiratory pressure (MEP) (measured with the
           MicroRPM handheld MEP device (Micro Direct Inc., Lewiston, ME)), peak cough flow (PCF)
           (measured with a handheld peak flow meter (BV Medical, Barrington, IL)), and FVC
           (measured with the Spirodoc spirometer and WinspiroPRO computer software (Medical
           International Research, New Berlin, WI)). All PFTs will be completed three times with
           PALS sitting in an upright seated position with a nose clip in line with standard PFT
           protocols. The highest of three measurements will be used for analyses.

      EMST Training: PALS will use the EMST-150 device (Aspire Products, Gainesville, Florida) or
      the Philips Threshold PEP trainer (Philips Respironics, Cedar Grove, New Jersey). During the
      experimental condition, EMST devices will be set to 50% of PALS' highest MEP from their
      baseline PFT assessment. During the control condition, no resistance will be added, and the
      loaded spring will be removed from the device. For both experimental conditions, PALS will
      undergo the following standard treatment protocol:

        1. PALS will complete five sets of five repetitions using an EMST device.

        2. For each repetition, PALS will be instructed to take a deep breath in and blow until the
           valve releases.

        3. Between repetitions, PALs will have 10-15 seconds of rest before the next repetition.

        4. After each set, PALS will rest for one minute before completing the next set.

      Post-treatment procedures: Following the EMST session with either the device set to 50% load
      or the sham device, PALS will undergo the same procedures (VF, HRCA, PFTs) as described above
      in steps 1-6 of the baseline procedures
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This study will be a prospective study with randomized experimental and control conditions. Patients with ALS will undergo the experimental and control conditions in random order on two separate days within a two-week time frame.
primary purpose: Treatment
masking: Double (Participant, Care Provider)
masking description: During the experimental condition, expiratory muscle strength training (EMST) devices will be set to 50% of patients with ALS' highest maximum expiratory pressure from their baseline pulmonary function test assessment. During the control condition, no resistance will be added, and the loaded spring will be removed from the device. For both experimental conditions, patients with ALS will be blinded to condition.
measure: Change in forced vital capacity (FVC) between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function.
measure: Change in forced vital capacity (FVC) between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function.
measure: Change in peak cough flow (PCF) between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: PCF is a measure of air flow during a cough.
measure: Change in peak cough flow (PCF) between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: PCF is a measure of air flow during a cough.
measure: Change in maximum expiratory pressure (MEP) between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out
measure: Change in maximum expiratory pressure (MEP) between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out
measure: Change in temporal kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second)
measure: Change in temporal kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second)
measure: Change in spatial kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels)
measure: Change in spatial kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels)
measure: Change in Modified Barium Swallow Impairment Profile (MBSImP) scores of swallowing between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing
measure: Change in Modified Barium Swallow Impairment Profile (MBSImP) scores of swallowing between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing
measure: Change in high resolution cervical auscultation (HRCA) signal features between pre and post expiratory muscle strength training (EMST) experimental session
time frame: pre and post EMST experimental session, up to 2 weeks
description: Feature extraction and analyses from HRCA will be completed before and after each EMST session and compared to VF to determine whether HRCA can detect fatigue related changes in swallow function.
measure: Change in high resolution cervical auscultation (HRCA) signal features between pre and post expiratory muscle strength training (EMST) sham session
time frame: pre and post EMST sham session, up to 2 weeks
description: Feature extraction and analyses from HRCA will be completed before and after each EMST session and compared to VF to determine whether HRCA can detect fatigue related changes in swallow function.
arm group label: Experimental, then sham
arm group type: Experimental
description: Patients with ALS in the experimental, then sham arm will undergo an expiratory muscle strength training (EMST) session with a device set to 50% of patients with ALS' highest maximum expiratory pressure from their baseline pulmonary function test assessment during their first study visit. Then, during their second study visit, patients with ALS will undergo an EMST session with a device set to 0% resistance.
arm group label: Sham, then experimental
arm group type: Experimental
description: Patients with ALS in the sham, then experimental arm will undergo an expiratory muscle strength training (EMST) session with a device set to 0% resistance during their first study visit. Then, during their second study visit, patients with ALS will undergo an EMST session with a device set to 50% of patients with ALS' highest maximum expiratory pressure from their baseline pulmonary function test assessment.
intervention type: Device
intervention name: Experimental expiratory muscle strength training (EMST)
description: The experimental EMST will involve blowing into a device with a spring-loaded valve set to 50% of the patient with ALS' maximum expiratory pressure.
arm group label: Experimental, then sham
arm group label: Sham, then experimental
intervention type: Device
intervention name: Sham expiratory muscle strength training (EMST)
description: The sham EMST will involve blowing into a device without a spring-loaded valve (0% resistance).
arm group label: Experimental, then sham
arm group label: Sham, then experimental
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Cara A Donohue, MA CCC-SLP
role: Principal Investigator
affiliation: University of Pittsburgh
last name: James L Coyle, PhD
role: Study Chair
affiliation: University of Pittsburgh
facility: 
country: United States
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responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Cara Donohue
investigator title: MA CCC-SLP/PhD Student
mesh term: Dyspnea
mesh term: Respiration Disorders
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
sharing ipd: No