Fatigue in Patients With Amyotrophic Lateral Sclerosis

February 10, 2021 updated by: Cara Donohue

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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).

  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

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15260
        • University of Pittsburgh Medical Center Presbyterian Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

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
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.
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
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.
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
Time Frame: pre and post EMST experimental session, up to 2 weeks
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
Time Frame: pre and post EMST sham session, up to 2 weeks
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
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
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
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
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
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)
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
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)
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
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)
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
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)
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
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
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
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
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
Time Frame: pre and post EMST experimental session, up to 2 weeks
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
Time Frame: pre and post EMST sham session, up to 2 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cara Donohue

Investigators

  • Principal Investigator: Cara A Donohue, MA CCC-SLP, University of Pittsburgh
  • Study Chair: James L Coyle, PhD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 10, 2021

Primary Completion (Actual)

February 10, 2021

Study Completion (Actual)

February 10, 2021

Study Registration Dates

First Submitted

June 22, 2020

First Submitted That Met QC Criteria

July 7, 2020

First Posted (Actual)

July 13, 2020

Study Record Updates

Last Update Posted (Actual)

February 15, 2021

Last Update Submitted That Met QC Criteria

February 10, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY20060082

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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