Respiratory Muscle Training (RMT) in ALS

Moderate Intensity Respiratory Muscle Training (RMT) in ALS

Twelve adults with ALS will participate in a study involving four 3-week cycles of progressive respiratory muscle training (RMT). The investigators will measure maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) weekly. The investigators will obtain the majority of measurements of MIP and MEP during web-based telehealth visits. Participants will be stratified into 2 groups based on baseline inspiratory muscle strength as determined by maximum inspiratory pressure (MIP): six participants with minimal to no respiratory weakness (i.e., MIP ≥ 70% predicted) and six participants with mild to moderate inspiratory weakness (i.e., MIP 40-70% predicted).

Study Overview

• Status: Completed
• Conditions: ALS
• Intervention / Treatment: Device: Respiratory Muscle Training

Detailed Description

Twelve adults will participate in a single- subject A1-B-A2 study involving 4 visits to Duke over 24 weeks. The 6 week delayed start period (A1) will establish baseline status prior to initiation of RMT (B) and the follow-up period (A2) will determine detraining effects over 6 weeks of RMT withdrawal. Participants will complete four 3-week cycles of progressive RMT during the B phase. The investigators will measure MIP and MEP weekly. To reduce participant burden and enhance our ability to obtain repeated measures, the investigators will obtain 21 of 25 measurements of MIP and MEP during web-based telehealth visits.

Participants will complete a full assessment during the first study visit (M1) and receive training/instruction for obtaining MIP and MEP measurements at home with a portable, battery-powered digital pressure gauge manometer (MicroRPM Pressure Meter; Micro Direct). They will return to Duke for the pretest visit (M7), at which time a full assessment will be completed and RMT will commence. During the B phase, participants will complete 12-weeks of moderate intensity RMT, divided into four 3-week cycles, and participate in weekly web-based RMT therapy visits (M8-M18). Post-test assessment (M19) will occur immediately following completion of the 12-week RMT regimen. The investigators will measure MIP and MEP during RMT withdrawal via web-based telehealth visits (M20-24). Following the fourth and final on-site full assessment visit (M25), participants will return all equipment and will be offered the opportunity to initiate a clinical RMT regimen and receive follow-up care by Speech Pathology during future ALS Clinic visits.

Participants will be stratified into 2 groups based on baseline inspiratory muscle strength as determined by maximum inspiratory pressure (MIP): six participants with minimal to no respiratory weakness (i.e., MIP ≥ 70% predicted) and six participants with mild to moderate inspiratory weakness (i.e., MIP 40-70% predicted).

The primary outcomes are MIP and MEP. Secondary outcomes include peak cough flow (PCF) and sniff nasal inspiratory pressure (SNIP). Exploratory outcomes include the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS), Eating Assessment Tool - 10 Item (EAT-10), 36-Item Short Form Survey (SF36), World Health Organization Quality of Life-BREF (WHOQOL-BREF), and Communicative Effectiveness Survey-Revised (CES-R). Clinical spirometry data will be extracted from the participant's electronic medical record if available from a coinciding ALS Clinic visit that occurs +/- 5 days from the assessment visit.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Confirmed diagnosis of ALS
• Ability to follow directions for study participation
• Ability to successfully and independently complete RMT repetitions at a minimum pressure-threshold target equal to 30% of MIP or MEP
• Ability to complete telehealth visits using a smartphone or computer with video capabilities
• Ability to complete a home-RMT regimen

Exclusion Criteria:

• MIP < 40 cmH20
• Presence of a tracheostomy
• Use of non-invasive or invasive ventilation when awake
• Participant or caregiver(s) inability to manipulate respiratory pressure meter, the RMT device, or calibration equipment for home training
• Inability to complete RMT repetitions successfully
• Concomitant neurologic or neurodegenerative conditions (e.g. stroke, dementia) or other serious conditions that would prevent meaningful study participation as determined at the discretion of the principal investigator
• Inability to give legally effective consent
• Inability to read and understand English

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Minimal to No Respiratory Weakness; MIP ≥ 70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.	Device: Respiratory Muscle Training; Two commercially available pressure-threshold RMT devices that utilize a spring-loaded flange to provide resistance against inspiration and expiration independent of respiratory flow rate will be used to provide the necessary range of resistance. Each participant will use two RMT devices, one for IMT and one for EMT.; Other Names: EMST 150; Threshold IMT
Experimental: Mild to Moderate Inspiratory Weakness; MIP 40-70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.	Device: Respiratory Muscle Training; Two commercially available pressure-threshold RMT devices that utilize a spring-loaded flange to provide resistance against inspiration and expiration independent of respiratory flow rate will be used to provide the necessary range of resistance. Each participant will use two RMT devices, one for IMT and one for EMT.; Other Names: EMST 150; Threshold IMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients with Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT)	Safe, well-tolerated moderate intensity Respiratory Muscle Training (RMT) is defined as: RPE between 4-5 and <6; Pain rating <4 on a standard 0-10 scale 0 = rest, 1 = very easy, 2 = easy, 3 = moderate, 4 = somewhat hard, 5 = hard, 6 = harder, 7 = very hard, 8/9 = extremely hard, 10 = maximal; Accuracy >90% for the last 10 of 25 repetitions in a set; Behavioral observations indicate repetitions are well tolerated.	12 weeks
Percentage of Patients Able to Complete Respiratory Muscle Training (RMT)	Feasibility will be determined by the percent of patients able to complete the Respiratory Muscle Training	12 weeks
Magnitude of Change in Maximum Expiratory Pressure from Pre-test to Post-test	Magnitude of change for our primary outcome measures will be determined using Cohen's measure of effect size (d) as defined by the first equation for single-subject d provided by Busk and Serlin (1992). Simply stated, d is obtained by subtracting the mean of the first assessment from the mean of the second assessment, divided by the standard deviation of the first assessment. Effect size calculations will be determined to compare results from pre-test (M7) to post-test (M18). The investigators will use conservative interpretation guidelines for effect size calculations in which d < 0.6 is negligible, d ≥ 0.6 modest, d ≥ 1.0 large, and d ≥ 2.0 very large.	Baseline, 12 weeks
Magnitude of Change in Maximum Expiratory Pressure from Baseline to Withdrawal	Magnitude of change for our primary outcome measures will be determined using Cohen's measure of effect size (d) as defined by the first equation for single-subject d provided by Busk and Serlin (1992). Simply stated, d is obtained by subtracting the mean of the first assessment from the mean of the second assessment, divided by the standard deviation of the first assessment. Effect size calculations will be determined to compare results from (M0-M5) to withdrawal (M19-M24). The investigators will use conservative interpretation guidelines for effect size calculations in which d < 0.6 is negligible, d ≥ 0.6 modest, d ≥ 1.0 large, and d ≥ 2.0 very large.	Baseline, 24 weeks
Magnitude of Change in Maximum Inspiratory Pressure from Pre-test to Post-test	Magnitude of change for our primary outcome measures will be determined using Cohen's measure of effect size (d) as defined by the first equation for single-subject d provided by Busk and Serlin (1992). Simply stated, d is obtained by subtracting the mean of the first assessment from the mean of the second assessment, divided by the standard deviation of the first assessment. Effect size calculations will be determined to compare results from pre-test (M7) to post-test (M18). The investigators will use conservative interpretation guidelines for effect size calculations in which d < 0.6 is negligible, d ≥ 0.6 modest, d ≥ 1.0 large, and d ≥ 2.0 very large.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Cough Flow in L/min	Effective peak cough flow in healthy subjects exceeds values of 360 to 400 L/min. PCF is measured at baseline, visit 7, visit 18 and visit 24. The overall change from baseline to visit 24 will be measured.	Baseline, 7 weeks, 18 weeks, 24 weeks
Change in Sniff Nasal Inspiratory Pressure	The sniff nasal inspiratory pressure (SNIP) consists in the measurement of pressure through an occluded nostril during sniffs performed through the contralateral nostril. SNIP is measured through a plug occluding one nostril during sniffs through the contralateral nostril. A plateau in pressure is reached after 5-10 sniffs in most individuals 1. For SNIP measurement, 10 sniffs are usually performed. The SNIP is measured at baseline, visit 7, visit 18 and visit 24. The overall change from baseline to visit 24 will be measured.	Baseline, 7 weeks, 18 weeks, 24 weeks

Collaborators and Investigators

• Sponsor: Duke University

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2020
• Primary Completion (Actual): November 29, 2022
• Study Completion (Actual): November 29, 2022

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: January 8, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 25, 2023
• Last Update Submitted That Met QC Criteria: January 23, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: Pro00103777

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