Fatigue in Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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). The ALS functional rating scale revised (ALSFRS-R) (an instrument used to assess changes in functional status over time in PALS), will be completed. 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. 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. 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. 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. 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: PALS will complete five sets of five repetitions using an EMST device. For each repetition, PALS will be instructed to take a deep breath in and blow until the valve releases. Between repetitions, PALs will have 10-15 seconds of rest before the next repetition. 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

Official Title
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Quantifying Fatigue of the Respiratory and Swallowing Musculature in Patients With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis, Dysphagia, Dyspnea, Respiration Disorders

Intervention / Treatment
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* Device: Experimental expiratory muscle strength training (EMST)
* Device: Sham expiratory muscle strength training (EMST)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of ALS defined as possible, probable, or definite by a neurologist using the El Escorial criteria FVC>65% predicted adequate cognition as defined by a score of >10 on the ALS Cognitive Behavioral Screen adequate labial seal for completing pulmonary function tests and expiratory muscle strength training (EMST) on a regular/thin liquid diet no allergies to barium not oxygen-dependent no tracheostomy/ mechanical ventilation no history of other neurological or respiratory disorders no history of smoking no history of head and neck cancer or other major head/neck surgery or radiation therapy. Exclusion Criteria: FVC<65% predicted inadequate cognition as defined by a score of <10 on the ALS Cognitive Behavioral Screen -inadequate labial seal for completing pulmonary function tests and expiratory muscle strength training (EMST) not on a regular/thin liquid diet allergies to barium oxygen-dependent presence of tracheostomy/dependent on mechanical ventilation history of other neurological or respiratory disorders history of smoking history of head and neck cancer or other major head/neck surgery or radiation therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental, then sham<br>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. | Device: Experimental expiratory muscle strength training (EMST)<br>* 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.<br>Device: Sham expiratory muscle strength training (EMST)<br>* The sham EMST will involve blowing into a device without a spring-loaded valve (0% resistance).<br>|
| Experimental: Sham, then experimental<br>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. | Device: Experimental expiratory muscle strength training (EMST)<br>* 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.<br>Device: Sham expiratory muscle strength training (EMST)<br>* The sham EMST will involve blowing into a device without a spring-loaded valve (0% resistance).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in forced vital capacity (FVC) between pre and post expiratory muscle strength training (EMST) experimental session | FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function. | pre and post EMST experimental session, up to 2 weeks | 
| Change in forced vital capacity (FVC) between pre and post expiratory muscle strength training (EMST) sham session | FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function. | pre and post EMST sham session, up to 2 weeks | 
| Change in peak cough flow (PCF) between pre and post expiratory muscle strength training (EMST) experimental session | PCF is a measure of air flow during a cough. | pre and post EMST experimental session, up to 2 weeks | 
| Change in peak cough flow (PCF) between pre and post expiratory muscle strength training (EMST) sham session | PCF is a measure of air flow during a cough. | pre and post EMST sham session, up to 2 weeks | 
| Change in maximum expiratory pressure (MEP) between pre and post expiratory muscle strength training (EMST) experimental session | Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out | pre and post EMST experimental session, up to 2 weeks | 
| Change in maximum expiratory pressure (MEP) between pre and post expiratory muscle strength training (EMST) sham session | Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out | pre and post EMST sham session, up to 2 weeks | 
| Change in temporal kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) experimental session | Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second) | pre and post EMST experimental session, up to 2 weeks | 
| Change in temporal kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) sham session | Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second) | pre and post EMST sham session, up to 2 weeks | 
| Change in spatial kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) experimental session | Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels) | pre and post EMST experimental session, up to 2 weeks | 
| Change in spatial kinematic measures of swallowing between pre and post expiratory muscle strength training (EMST) sham session | Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels) | pre and post EMST sham session, up to 2 weeks | 
| Change in Modified Barium Swallow Impairment Profile (MBSImP) scores of swallowing between pre and post expiratory muscle strength training (EMST) experimental session | The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing | pre and post EMST experimental session, up to 2 weeks | 
| Change in Modified Barium Swallow Impairment Profile (MBSImP) scores of swallowing between pre and post expiratory muscle strength training (EMST) sham session | The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing | pre and post EMST sham session, up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in high resolution cervical auscultation (HRCA) signal features between pre and post expiratory muscle strength training (EMST) experimental session | 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. | pre and post EMST experimental session, up to 2 weeks | 
| Change in high resolution cervical auscultation (HRCA) signal features between pre and post expiratory muscle strength training (EMST) sham session | 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. | pre and post EMST sham session, up to 2 weeks |