Trial Outcomes & Findings for Respiratory Muscle Training (RMT) in ALS (NCT NCT04224961)
NCT ID: NCT04224961
Last Updated: 2026-01-29
Results Overview
Safe, well-tolerated moderate intensity Respiratory Muscle Training (RMT) is in part defined as an RPE between 4-5 and \<6. The RPE is a way of measuring physical activity intensity level. Perceived exertion is how hard the participant feels like their body is working. 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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
9 participants
Primary outcome timeframe
12 weeks
Results posted on
2026-01-29
Participant Flow
Participant milestones
| Measure |
Minimal to No Respiratory Weakness
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
1
|
|
Overall Study
COMPLETED
|
7
|
0
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Minimal to No Respiratory Weakness
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
Respiratory Muscle Training (RMT) in ALS
Baseline characteristics by cohort
| Measure |
Minimal to No Respiratory Weakness
n=8 Participants
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
n=1 Participants
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.4 years
STANDARD_DEVIATION 11.7 • n=35 Participants
|
73.0 years
STANDARD_DEVIATION 0 • n=4328 Participants
|
62.7 years
STANDARD_DEVIATION 11.6 • n=8687 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
3 Participants
n=8687 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
6 Participants
n=8687 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
9 Participants
n=8687 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
9 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
|
Region of Enrollment
United States
|
8 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
9 Participants
n=8687 Participants
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Participants who completed the study.
Safe, well-tolerated moderate intensity Respiratory Muscle Training (RMT) is in part defined as an RPE between 4-5 and \<6. The RPE is a way of measuring physical activity intensity level. Perceived exertion is how hard the participant feels like their body is working. 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.
Outcome measures
| Measure |
Minimal to No Respiratory Weakness
n=7 Participants
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Number of Participants With Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT) as Measured by Rating of Perceived Exertion (RPE)
|
4 Participants
|
—
|
PRIMARY outcome
Timeframe: 12 weeksPopulation: Participants who completed the study.
Safe, well-tolerated moderate intensity Respiratory Muscle Training (RMT) is in part defined as a pain rating of \<4 on a standard 0-10 scale, where 0 = no pain and 10 = the worst pain possible.
Outcome measures
| Measure |
Minimal to No Respiratory Weakness
n=7 Participants
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Number of Participants With Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT) as Measured by Pain Score
|
6 Participants
|
—
|
PRIMARY outcome
Timeframe: 12 weeksFeasibility will be determined by the number of participants able to complete the Respiratory Muscle Training
Outcome measures
| Measure |
Minimal to No Respiratory Weakness
n=8 Participants
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
n=1 Participants
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Number of Participants Able to Complete Respiratory Muscle Training (RMT)
|
7 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: from pre-test (week 7) to post-test (week 18)Population: Participants who completed the study.
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.
Outcome measures
| Measure |
Minimal to No Respiratory Weakness
n=7 Participants
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Magnitude of Change in Maximum Inspiratory Pressure From Pre-test to Post-test as Determined by Cohen's Measure of Effect Size
Negligible
|
5 Participants
|
—
|
|
Magnitude of Change in Maximum Inspiratory Pressure From Pre-test to Post-test as Determined by Cohen's Measure of Effect Size
Modest
|
1 Participants
|
—
|
|
Magnitude of Change in Maximum Inspiratory Pressure From Pre-test to Post-test as Determined by Cohen's Measure of Effect Size
Large
|
1 Participants
|
—
|
PRIMARY outcome
Timeframe: from baseline to withdrawal (up to week 24)Population: Participants who completed the study.
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 baseline (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.
Outcome measures
| Measure |
Minimal to No Respiratory Weakness
n=7 Participants
Maximum inspiratory pressure (MIP) ≥ 70% predicted. Complete home-based respiratory muscle training (RMT) program and participate in weekly web-based RMT therapy sessions.
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 inspiratory muscle training (IMT) and one for expiratory muscle training (EMT).
|
Mild to Moderate Inspiratory Weakness
MIP 40-70% predicted. Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Magnitude of Change in Maximum Expiratory Pressure From Baseline to Withdrawal as Determined by Cohen's Measure of Effect Size
Negligible
|
5 Participants
|
—
|
|
Magnitude of Change in Maximum Expiratory Pressure From Baseline to Withdrawal as Determined by Cohen's Measure of Effect Size
Large
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, 7 weeks, 18 weeks, 24 weeksPopulation: Data not collected due to COVID restrictions, which prevented study staff from accessing the participants in order to perform the measurement. There are no plans to collect this data in the future.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline, 7 weeks, 18 weeks, 24 weeksPopulation: Data not collected due to COVID restrictions, which prevented study staff from accessing the participants in order to perform the measurement. There are no plans to collect this data in the future.
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.
Outcome measures
Outcome data not reported
Adverse Events
Minimal to No Respiratory Weakness
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Mild to Moderate Inspiratory Weakness
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Minimal to No Respiratory Weakness
n=8 participants at risk
MIP ≥ 70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
Mild to Moderate Inspiratory Weakness
n=1 participants at risk
MIP 40-70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory decline
|
0.00%
0/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
100.0%
1/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
Other adverse events
| Measure |
Minimal to No Respiratory Weakness
n=8 participants at risk
MIP ≥ 70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
Mild to Moderate Inspiratory Weakness
n=1 participants at risk
MIP 40-70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions.
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.
|
|---|---|---|
|
General disorders
Dysphonia
|
0.00%
0/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
100.0%
1/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
Musculoskeletal and connective tissue disorders
Neck weakness/tightness
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
100.0%
1/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
General disorders
Seasonal allergies/headache
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
0.00%
0/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
General disorders
Dizziness
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
0.00%
0/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
0.00%
0/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
Infections and infestations
COVID diagnosis
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
0.00%
0/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
General disorders
Fall without injury
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
0.00%
0/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis
|
12.5%
1/8 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
0.00%
0/1 • Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place