Amyotrophic Lateral SclerosisNCT04468191
Fatigue in Patients With Amyotrophic Lateral Sclerosis
A study testing Experimental expiratory muscle strength training (EMST) in people with Amyotrophic Lateral Sclerosis and Dysphagia, run by Cara Donohue at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Dysphagia, Dyspnea
- What is being tested?
- Experimental expiratory muscle strength training (EMST)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2021to 10 Feb 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center Presbyterian Hospital
Pittsburgh, Pennsylvania, 15260
About this study
Official title: Quantifying Fatigue of the Respiratory and Swallowing Musculature in Patients With Amyotrophic Lateral Sclerosis
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.
Read the detailed description
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
- Being tested
- Experimental expiratory muscle strength training (EMST), Sham expiratory muscle strength training (EMST)
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Deglutition Disorders, Dyspnea, Respiration Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental expiratory muscle strength training (EMST)Device
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.
Sham expiratory muscle strength training (EMST)Device
The sham EMST will involve blowing into a device without a spring-loaded valve (0% resistance).
| Study group | Role | What they receive |
|---|---|---|
| Experimental, then sham | Experimental | 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. Receives: Device: Experimental expiratory muscle strength training (EMST); Device: Sham expiratory muscle strength training (EMST) |
| Sham, then experimental | Experimental | 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. Receives: Device: Experimental expiratory muscle strength training (EMST); Device: Sham expiratory muscle strength training (EMST) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: pre and post EMST sham session, up to 2 weeks
Secondary outcomes (2)
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.
Measured: 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.
Measured: pre and post EMST sham session, up to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2020
- Study start10 Feb 2021
- Primary completion10 Feb 2021
- Study completion10 Feb 2021
Why it stopped: COVID-19 pandemic restrictions for data collection
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (85)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Care provider
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Donohue
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Cara Donohue, University of Pittsburgh
- Investigators
- Cara A Donohue, MA CCC-SLP, Principal investigator, University of PittsburghJames L Coyle, PhD, Study chair, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04468191
- Sponsor's protocol ID
- STUDY20060082
- Status last verified
- Feb 2021
- First submitted
- 22 Jun 2020
- Last updated
- 15 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Ball LJ, Willis A, Beukelman DR, Pattee GL. A protocol for identification of early bulbar signs in amyotrophic lateral sclerosis. J Neurol Sci. 2001 Oct 15;191(1-2):43-53. doi: 10.1016/s0022-510x(01)00623-2.
PubMed 11676991Kuhnlein P, Gdynia HJ, Sperfeld AD, Lindner-Pfleghar B, Ludolph AC, Prosiegel M, Riecker A. Diagnosis and treatment of bulbar symptoms in amyotrophic lateral sclerosis. Nat Clin Pract Neurol. 2008 Jul;4(7):366-74. doi: 10.1038/ncpneuro0853. Epub 2008 Jun 17.
PubMed 18560390da Costa Franceschini A, Mourao LF. Dysarthria and dysphagia in Amyotrophic Lateral Sclerosis with spinal onset: a study of quality of life related to swallowing. NeuroRehabilitation. 2015;36(1):127-34. doi: 10.3233/NRE-141200.
PubMed 25547774Paris G, Martinaud O, Petit A, Cuvelier A, Hannequin D, Roppeneck P, Verin E. Oropharyngeal dysphagia in amyotrophic lateral sclerosis alters quality of life. J Oral Rehabil. 2013 Mar;40(3):199-204. doi: 10.1111/joor.12019. Epub 2012 Dec 27.
PubMed 23278936Andrews JA, Meng L, Kulke SF, Rudnicki SA, Wolff AA, Bozik ME, Malik FI, Shefner JM. Association Between Decline in Slow Vital Capacity and Respiratory Insufficiency, Use of Assisted Ventilation, Tracheostomy, or Death in Patients With Amyotrophic Lateral Sclerosis. JAMA Neurol. 2018 Jan 1;75(1):58-64. doi: 10.1001/jamaneurol.2017.3339.
PubMed 29181534Plowman EK, Watts SA, Tabor L, Robison R, Gaziano J, Domer AS, Richter J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis. Muscle Nerve. 2016 Jun;54(1):48-53. doi: 10.1002/mus.24990. Epub 2016 Mar 3.
PubMed 26599236Tabor LC, Rosado KM, Robison R, Hegland K, Humbert IA, Plowman EK. Respiratory training in an individual with amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2016 Sep 1;3(10):819-823. doi: 10.1002/acn3.342. eCollection 2016 Oct.
PubMed 27752517Robison R, Tabor-Gray LC, Wymer JP, Plowman EK. Combined respiratory training in an individual with C9orf72 amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2018 Aug 21;5(9):1134-1138. doi: 10.1002/acn3.623. eCollection 2018 Sep.
PubMed 30250869Plowman EK, Tabor-Gray L, Rosado KM, Vasilopoulos T, Robison R, Chapin JL, Gaziano J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial. Muscle Nerve. 2019 Jan;59(1):40-46. doi: 10.1002/mus.26292. Epub 2018 Nov 29.
PubMed 29981250de Almeida JP, Silvestre R, Pinto AC, de Carvalho M. Exercise and amyotrophic lateral sclerosis. Neurol Sci. 2012 Feb;33(1):9-15. doi: 10.1007/s10072-011-0921-9. Epub 2012 Jan 7.
PubMed 22228269Harkawik, R., Coyle, J.L. Exercise for better ALS management? ASHA Leader. 2012; 17(11). http://leader.pubs.asha.org/article.aspx?articleid=2292004
Casaburi R. Principles of exercise training. Chest. 1992 May;101(5 Suppl):263S-267S.
PubMed 1576847Gibbons C, Pagnini F, Friede T, Young CA. Treatment of fatigue in amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2018 Jan 2;1(1):CD011005. doi: 10.1002/14651858.CD011005.pub2.
PubMed 29293261Dudik JM, Coyle JL, Sejdic E. Dysphagia Screening: Contributions of Cervical Auscultation Signals and Modern Signal-Processing Techniques. IEEE Trans Hum Mach Syst. 2015 Aug;45(4):465-477. doi: 10.1109/THMS.2015.2408615.
PubMed 26213659Jestrovic I, Dudik JM, Luan B, Coyle JL, Sejdic E. The effects of increased fluid viscosity on swallowing sounds in healthy adults. Biomed Eng Online. 2013 Sep 10;12:90. doi: 10.1186/1475-925X-12-90.
PubMed 24020398
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantifying Fatigue of the Respiratory and Swallowing Musculature in Patients With Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT04468191
- Acronym / sponsor ID
- STUDY20060082
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: COVID-19 pandemic restrictions for data collection
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cara DonohueUniversity, hospital or other
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- 10 Feb 2021 (actual)
- Study completion
- 10 Feb 2021 (actual)
- First posted
- 13 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Experimental, then sham | Experimental | Device: Experimental expiratory muscle strength training (EMST), Device: Sham expiratory muscle strength training (EMST)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. |
| Sham, then experimental | Experimental | Device: Experimental expiratory muscle strength training (EMST), Device: Sham expiratory muscle strength training (EMST)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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental expiratory muscle strength training (EMST)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. | Device | Experimental, then sham, Sham, then experimental |
| Sham expiratory muscle strength training (EMST)The sham EMST will involve blowing into a device without a spring-loaded valve (0% resistance). | Device | Experimental, then sham, Sham, then experimental |
Primary outcome
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
FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function.
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
FVC is a measure of the total amount of air that can be breathed out during a pulmonary function test to measure lung function.
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
PCF is a measure of air flow during a cough.
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
PCF is a measure of air flow during a cough.
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
Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out
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
Maximum expiratory pressure is a measure of strength of the respiratory muscles when breathing out
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
Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second)
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
Timing measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in frames per second)
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
Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels)
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
Distance measures of physiological events that occur during swallowing based on videofluoroscopic swallow studies (measured in pixels)
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
The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing
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
The MBSImP is a standardized clinical ordinal, categorical rating tool of 17 physiological components of swallowing
2 secondary outcomes
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
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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
- Background: PubMed 11676991Ball LJ, Willis A, Beukelman DR, Pattee GL. A protocol for identification of early bulbar signs in amyotrophic lateral sclerosis. J Neurol Sci. 2001 Oct 15;191(1-2):43-53. doi: 10.1016/s0022-510x(01)00623-2.
- Background: PubMed 18560390Kuhnlein P, Gdynia HJ, Sperfeld AD, Lindner-Pfleghar B, Ludolph AC, Prosiegel M, Riecker A. Diagnosis and treatment of bulbar symptoms in amyotrophic lateral sclerosis. Nat Clin Pract Neurol. 2008 Jul;4(7):366-74. doi: 10.1038/ncpneuro0853. Epub 2008 Jun 17.
- Background: PubMed 25547774da Costa Franceschini A, Mourao LF. Dysarthria and dysphagia in Amyotrophic Lateral Sclerosis with spinal onset: a study of quality of life related to swallowing. NeuroRehabilitation. 2015;36(1):127-34. doi: 10.3233/NRE-141200.
- Background: PubMed 23278936Paris G, Martinaud O, Petit A, Cuvelier A, Hannequin D, Roppeneck P, Verin E. Oropharyngeal dysphagia in amyotrophic lateral sclerosis alters quality of life. J Oral Rehabil. 2013 Mar;40(3):199-204. doi: 10.1111/joor.12019. Epub 2012 Dec 27.
- Background: PubMed 29181534Andrews JA, Meng L, Kulke SF, Rudnicki SA, Wolff AA, Bozik ME, Malik FI, Shefner JM. Association Between Decline in Slow Vital Capacity and Respiratory Insufficiency, Use of Assisted Ventilation, Tracheostomy, or Death in Patients With Amyotrophic Lateral Sclerosis. JAMA Neurol. 2018 Jan 1;75(1):58-64. doi: 10.1001/jamaneurol.2017.3339.
- Background: PubMed 26599236Plowman EK, Watts SA, Tabor L, Robison R, Gaziano J, Domer AS, Richter J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis. Muscle Nerve. 2016 Jun;54(1):48-53. doi: 10.1002/mus.24990. Epub 2016 Mar 3.
- Background: PubMed 27752517Tabor LC, Rosado KM, Robison R, Hegland K, Humbert IA, Plowman EK. Respiratory training in an individual with amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2016 Sep 1;3(10):819-823. doi: 10.1002/acn3.342. eCollection 2016 Oct.
- Background: PubMed 30250869Robison R, Tabor-Gray LC, Wymer JP, Plowman EK. Combined respiratory training in an individual with C9orf72 amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2018 Aug 21;5(9):1134-1138. doi: 10.1002/acn3.623. eCollection 2018 Sep.
- Background: PubMed 29981250Plowman EK, Tabor-Gray L, Rosado KM, Vasilopoulos T, Robison R, Chapin JL, Gaziano J, Vu T, Gooch C. Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial. Muscle Nerve. 2019 Jan;59(1):40-46. doi: 10.1002/mus.26292. Epub 2018 Nov 29.
- Background: PubMed 22228269de Almeida JP, Silvestre R, Pinto AC, de Carvalho M. Exercise and amyotrophic lateral sclerosis. Neurol Sci. 2012 Feb;33(1):9-15. doi: 10.1007/s10072-011-0921-9. Epub 2012 Jan 7.
- BackgroundHarkawik, R., Coyle, J.L. Exercise for better ALS management? ASHA Leader. 2012; 17(11). http://leader.pubs.asha.org/article.aspx?articleid=2292004
- Background: PubMed 1576847Casaburi R. Principles of exercise training. Chest. 1992 May;101(5 Suppl):263S-267S.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cara A Donohue, MA CCC-SLP principal investigator
University of Pittsburgh
James L Coyle, PhD study chair
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Experimental expiratory muscle strength training (EMST) in people with Amyotrophic Lateral Sclerosis and Dysphagia, run by Cara Donohue at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04468191, which also lists 85 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2021; AzTrials last refreshed its copy on 6 Nov 2026.