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The goal of this clinical trial is to learn how doing mechanical insufflation (MI) using a mechanical insufflator-exsufflator (MI-E) device affects breathing in early amyotrophic lateral sclerosis (ALS). This will be a single-center, single-arm study of MI in 20 patients with ALS at Penn.
Based on prior research, we believe that 6-months of MI may slow decline in cough strength, measured as peak cough flow (PCF).
Participants will perform MI using a device designed for mechanical insufflation-exsufflation (MI-E) known as the BiWaze Cough system. The BiWaze Cough is used for mucus clearance . It is connected to tubing and mouthpiece (or mask). The device will use programmed pressure and timing settings. An insufflation includes inflating the lungs for a maximal size inhalation before exhaling. The daily routine for the device includes 5 sets of 5 insufflations twice daily.
Researchers will compare how use of MI in early ALS affects peak cough flow compared to 20 subjects who did not use MI in early ALS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mechanical insufflation | Experimental | Participants will be asked to perform mechanical insufflation using the BiWaze cough device as 5 sets of 5 insufflations twice daily for 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mechanical insufflation | Device | Mechanical insufflation (MI) is a chest physiotherapy exercise that will be performed using a type of mechanical insufflator-exsufflator (MI-E) known as the BiWaze Cough device. The device connects to a tube that can interface with a patient using either a facemask or mouthpiece. Mechanical insufflation is a chest physiotherapy exercise that passively inflates the chest with positive pressure that is delivered in coordination with the patient's own inspiratory timing until maximal inflation capacity (MIC), determined by the patient or maximal chest rise on visual inspection. At MIC, the patient passively exhales, which completes one "cycle". Prior literature has used a "dose" of 5 sets of 5 cycles once or twice daily. The maneuver is usually performed with assistance of a caregiver to hold the mask or mouthpiece in place. |
| Measure | Description | Time Frame |
|---|---|---|
| peak cough flow (PCF) | PCF in liters/minute as measured by use of a peak flow meter while the patient is in a seated upright position. An alternative device for measuring PCF can be the use of a handheld spirometer and using the measured peak expiratory flow by multiplying by 60 to convert from liters/second to liters/minute. The subject must be seated in an upright position and the interface must include a mouthpiece or an oronasal mask. Subjects are asked to perform a deep inhalation followed by a maximal cough. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Forced vital capacity (FVC) | Defined as maximal volume, in liters, that a person can exhale forcefully after a complete inhalation. Measured using a spirometer connected to a face mask or mouthpiece in the sitting and upright position. | 6 months |
| Maximal inspiratory pressure (MIP) |
| Measure | Description | Time Frame |
|---|---|---|
| Time to start of non-invasive ventilation | Defined by the time period between enrollment for the MI trial and date of prescription for non-invasive ventilation Non-invasive ventilation start date will be defined by date of prescription for non-invasive ventilation as recorded in the medical record or patient-reported date if a prescription is not recorded in the medical record. | 1 year |
Inclusion Criteria:
Exclusion Criteria:
Age <18 years old.
Inability to perform a cough peak flow or spirometry manuever
Current use of non-invasive ventilation (NIV), bi-level positive pressure ventilation, or "Bi-PAP" or physician prescribing NIV on day of potential enrollment.
Current use of MI-E (also known as a "cough assist device") for airway clearance. Please note that patients can start use of a MI-E device subsequent to enrollment while currently being followed for the study.
Active enrollment in hospice.
Current tracheostomy.
Presence of cognitive dysfunction that would impair ability to complete study procedures, as determined by neurology attending physician.
Absence of an able and willing caregiver to assist with MI twice daily as specified in the protocol.
Pregnancy
Medical history of any of the following:
Current smoker or tobacco use within the last 30 days.
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| Name | Affiliation | Role |
|---|---|---|
| Jason Ackrivo, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25845857 | Background | Kaminska M, Browman F, Trojan DA, Genge A, Benedetti A, Petrof BJ. Feasibility of Lung Volume Recruitment in Early Neuromuscular Weakness: A Comparison Between Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, and Postpolio Syndrome. PM R. 2015 Jul;7(7):677-684. doi: 10.1016/j.pmrj.2015.04.001. Epub 2015 Apr 3. | |
| 26599476 | Background |
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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 | Sep 29, 2025 |
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single-center, single-arm feasibility pilot study of in 20 patients with ALS.
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|
Defined as the maximum pressure, in cmH2O, generated when the subject exhales as much air as possible and then immediately inhales as forcefully as possible. |
| 6 months |
| Maximal expiratory pressure (MEP) | Defined as the maximum pressure, in cmH2O, generated when the subject inhales as much air as possible and then immediately exhales as forcefully as possible. Measured using a hand-held manual or digital manometer connected to a mouthpiece or mask in the sitting and upright position. | 6 months |
| Maximum insufflation capacity (MIC) | Defined as exhaled volume, in liters, immediately following a MI maneuver to maximum insufflation capacity. Measured using a spirometer connected to a face mask or mouthpiece, in the sitting and upright position. | 6 months |
| Maximum insufflation capacity assisted peak cough flow | Defined as the peak cough flow generated from MIC. Lungs are inflated to MIC using MI and before the subject exhales they insert a peak flow meter in their mouth and follow with a peak cough flow as described above. | 6 months |
| MIC-FVC difference | defined by subtracting the FVC from the MIC | 6 months |
| Transcutaneous carbon dioxide | Defined as the average value in mmHg from a daytime in-clinic measurement over a 15-minute transcutaneous recording. Measured using a Sentec transcutaneous digital monitoring system while the subject is sitting upright in a chair or wheelchair. The transcutaneous sensor can be placed on the subject forehead, cheek, or earlobe. | 6 months |
| ALS Functional Rating Scale - Revised (ALSFRS-R) dyspnea and orthopnea scores | The ALSFRS-R is a 12-item standardized questionnaire to assess the motor function status of an individual with ALS. The ALSFRS-R is assessed by a research staff member who has been certified for performance of the ALSFRS-R. The dyspnea score is one of the questions focusing on level of shortness of breath, scored on a scale of 0 to 4, with 4 being no symptoms at all and 0 being severely symptomatic with consideration of mechanical respiratory support. The orthopnea score is one of the questions focused on breathing symptoms and difficulty sleeping while lying supine, scored on a scale of 0 to 4, with 4 being no symptoms at all and 0 being severely symptomatic with inability to sleep. | 6 months |
| Global rate of change score for peak cough flow | The global rate of change score for the peak cough flow will ask patients how effective they think their cough is today by rating it on a Likert scale from -7 (extremely impaired) to +7 (extremely strong). | 6 months |
| Tracheostomy free survival time | Defined by the time period between enrollment for the MI trial and death as long as the subject never had a tracheostomy placed. Death date will be determined by family report, electronic medical record review, or publicly available obituaries. Tracheostomy placement will be determined by patient or family report; or as documented in the electronic medical record. | 1 year |
| Katz SL, Barrowman N, Monsour A, Su S, Hoey L, McKim D. Long-Term Effects of Lung Volume Recruitment on Maximal Inspiratory Capacity and Vital Capacity in Duchenne Muscular Dystrophy. Ann Am Thorac Soc. 2016 Feb;13(2):217-22. doi: 10.1513/AnnalsATS.201507-475BC. |
| 22421625 | Background | McKim DA, Katz SL, Barrowman N, Ni A, LeBlanc C. Lung volume recruitment slows pulmonary function decline in Duchenne muscular dystrophy. Arch Phys Med Rehabil. 2012 Jul;93(7):1117-22. doi: 10.1016/j.apmr.2012.02.024. Epub 2012 Mar 12. |
| 27630091 | Background | Chiou M, Bach JR, Jethani L, Gallagher MF. Active lung volume recruitment to preserve vital capacity in Duchenne muscular dystrophy. J Rehabil Med. 2017 Jan 19;49(1):49-53. doi: 10.2340/16501977-2144. |
| 14610141 | Background | Mustfa N, Aiello M, Lyall RA, Nikoletou D, Olivieri D, Leigh PN, Davidson AC, Polkey MI, Moxham J. Cough augmentation in amyotrophic lateral sclerosis. Neurology. 2003 Nov 11;61(9):1285-7. doi: 10.1212/01.wnl.0000092018.56823.02. |
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| 19822872 | Background | Miller RG, Jackson CE, Kasarskis EJ, England JD, Forshew D, Johnston W, Kalra S, Katz JS, Mitsumoto H, Rosenfeld J, Shoesmith C, Strong MJ, Woolley SC; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2009 Oct 13;73(15):1218-26. doi: 10.1212/WNL.0b013e3181bc0141. |
| 32658385 | Background | Sawnani H, Mayer OH, Modi AC, Pascoe JE, McConnell K, McDonough JM, Rutkowski AM, Hossain MM, Szczesniak R, Tadesse DG, Schuler CL, Amin R. Randomized trial of lung hyperinflation therapy in children with congenital muscular dystrophy. Pediatr Pulmonol. 2020 Sep;55(9):2471-2478. doi: 10.1002/ppul.24954. Epub 2020 Jul 20. |
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| 34949706 | Background | Stanojevic S, Kaminsky DA, Miller MR, Thompson B, Aliverti A, Barjaktarevic I, Cooper BG, Culver B, Derom E, Hall GL, Hallstrand TS, Leuppi JD, MacIntyre N, McCormack M, Rosenfeld M, Swenson ER. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J. 2022 Jul 13;60(1):2101499. doi: 10.1183/13993003.01499-2021. Print 2022 Jul. |
| 32387049 | Background | Shefner JM, Al-Chalabi A, Baker MR, Cui LY, de Carvalho M, Eisen A, Grosskreutz J, Hardiman O, Henderson R, Matamala JM, Mitsumoto H, Paulus W, Simon N, Swash M, Talbot K, Turner MR, Ugawa Y, van den Berg LH, Verdugo R, Vucic S, Kaji R, Burke D, Kiernan MC. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol. 2020 Aug;131(8):1975-1978. doi: 10.1016/j.clinph.2020.04.005. Epub 2020 Apr 19. No abstract available. |
| 28326313 | Background | Molgat-Seon Y, Hannan LM, Dominelli PB, Peters CM, Fougere RJ, McKim DA, Sheel AW, Road JD. Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness. ERJ Open Res. 2017 Mar 14;3(1):00135-2016. doi: 10.1183/23120541.00135-2016. eCollection 2017 Jan. |
| 23383293 | Background | Srour N, LeBlanc C, King J, McKim DA. Lung volume recruitment in multiple sclerosis. PLoS One. 2013;8(1):e56676. doi: 10.1371/journal.pone.0056676. Epub 2013 Jan 31. |
| Apr 1, 2026 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 24, 2025 | Apr 1, 2026 | ICF_001.pdf |
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D009468 | Neuromuscular Diseases |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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