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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minimal to No Respiratory Weakness | Experimental | MIP ≥ 70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions. |
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| Mild to Moderate Inspiratory Weakness | Experimental | MIP 40-70% predicted Complete home-based RMT program and participate in weekly web-based RMT therapy sessions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Respiratory Muscle Training | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT) as Measured by Rating of Perceived Exertion (RPE) | 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. | 12 weeks |
| Number of Participants With Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT) as Measured by Pain Score | 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. | 12 weeks |
| Number of Participants Able to Complete Respiratory Muscle Training (RMT) | Feasibility will be determined by the number of participants able to complete the Respiratory Muscle Training | 12 weeks |
| Magnitude of Change in Maximum Inspiratory Pressure From Pre-test to Post-test as Determined by Cohen's Measure of Effect Size | 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. | from pre-test (week 7) to post-test (week 18) |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Harrison Jones, PhD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27705 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT) as Measured by Rating of Perceived Exertion (RPE) | 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. | Participants who completed the study. | Posted | Count of Participants | Participants | 12 weeks |
|
Baseline to approximately 24 weeks
Adverse events/serious adverse events were systematically investigated at each study visit and recorded using REDCap.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Minimal to No Respiratory Weakness | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory decline | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysphonia | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Harrison N. Jones, PhD | Duke University | 919-681-1852 | harrison.jones@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 3, 2021 | Nov 13, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001945 | Breathing Exercises |
| ID | Term |
|---|---|
| D026441 | Mind-Body Therapies |
| D000529 | Complementary Therapies |
| D013812 | Therapeutics |
| D026241 | Exercise Movement Techniques |
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|
| Magnitude of Change in Maximum Expiratory Pressure From Baseline to Withdrawal as Determined by Cohen's Measure of Effect Size | 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. | from baseline to withdrawal (up to week 24) |
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 |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | 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. |
|
|
| Primary | Number of Participants With Safe, Well-tolerated Moderate Intensity Respiratory Muscle Training (RMT) as Measured by Pain Score | 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. | Participants who completed the study. | Posted | Count of Participants | Participants | 12 weeks |
|
|
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| Primary | Number of Participants Able to Complete Respiratory Muscle Training (RMT) | Feasibility will be determined by the number of participants able to complete the Respiratory Muscle Training | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| Primary | Magnitude of Change in Maximum Inspiratory Pressure From Pre-test to Post-test as Determined by Cohen's Measure of Effect Size | 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. | Participants who completed the study. | Posted | Count of Participants | Participants | from pre-test (week 7) to post-test (week 18) |
|
|
|
| Primary | Magnitude of Change in Maximum Expiratory Pressure From Baseline to Withdrawal as Determined by Cohen's Measure of Effect Size | 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. | Participants who completed the study. | Posted | Count of Participants | Participants | from baseline to withdrawal (up to week 24) |
|
|
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| Secondary | 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. | 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. | Posted | Baseline, 7 weeks, 18 weeks, 24 weeks |
|
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| Secondary | 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. | 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. | Posted | Baseline, 7 weeks, 18 weeks, 24 weeks |
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|
| 0 |
| 8 |
| 0 |
| 8 |
| 5 |
| 8 |
| EG001 | 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. | 0 | 1 | 1 | 1 | 1 | 1 |
| Neck weakness/tightness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Seasonal allergies/headache | General disorders | Systematic Assessment |
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| Dizziness | General disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| COVID diagnosis | Infections and infestations | Systematic Assessment |
|
| Fall without injury | General disorders | Systematic Assessment |
|
| Bronchitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D026741 |
| Physical Therapy Modalities |