Mechanical Insufflation in the Philadelphia Amyotrophic Lateral Sclerosis Cohort (MI-PALS) Study

Sponsor

University of Pennsylvania (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06119087

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis Chronic Respiratory Failure Airway Clearance Impairment Neuromuscular Diseases	Device: Mechanical insufflation	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

single-center, single-arm feasibility pilot study of in 20 patients with ALS.single-center, single-arm feasibility pilot study of in 20 patients with ALS.

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Mechanical Insufflation in the Philadelphia Amyotrophic Lateral Sclerosis Cohort (MI-PALS) Study

Anticipated Study Start Date :

Mar 1, 2024

Anticipated Primary Completion Date :

May 8, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mechanical insufflation Participants will be asked to perform mechanical insufflation using the BiWaze cough device as 5 sets of 5 insufflations twice daily for 6 months.	Device: Mechanical insufflation 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.

Arm

Intervention/Treatment

Experimental: Mechanical insufflation

Participants will be asked to perform mechanical insufflation using the BiWaze cough device as 5 sets of 5 insufflations twice daily for 6 months.

Device: Mechanical insufflation

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.

Outcome Measures

Primary Outcome Measures

peak cough flow (PCF) [6 months]
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.

Secondary Outcome Measures

Forced vital capacity (FVC) [6 months]
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.
Maximal inspiratory pressure (MIP) [6 months]
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.
Maximal expiratory pressure (MEP) [6 months]
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.
Maximum insufflation capacity (MIC) [6 months]
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.
Maximum insufflation capacity assisted peak cough flow [6 months]
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.
MIC-FVC difference [6 months]
defined by subtracting the FVC from the MIC
Transcutaneous carbon dioxide [6 months]
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.
ALS Functional Rating Scale - Revised (ALSFRS-R) dyspnea and orthopnea scores [6 months]
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.
Global rate of change score for peak cough flow [6 months]
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).

Other Outcome Measures

Time to start of non-invasive ventilation [1 year]
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.
Tracheostomy free survival time [1 year]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form.
Stated willingness to comply with all study procedures and availability for the duration of the study.
Age ≥18 years.
Diagnosed with amyotrophic lateral sclerosis using the Gold Coast Criteria.
Have an able and willing caregiver to assist with mechanical insufflation on a daily basis.
Willingness and ability to participate in study procedures.

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:
Recent hemoptysis
Recent barotrauma
History of emphysema of any kind (including bullous emphysema)
History of or known susceptibility to pneumothorax
History of or known susceptibility to pneumomediastinum
Chronic obstructive pulmonary disease
Uncontrolled asthma (defined as recent exacerbation requiring corticosteroids in the previous 30 days)
Symptomatic cardiomyopathy (heart failure) with left ventricular ejection fraction less than 50%
History of right heart failure or pulmonary hypertension
Current smoker or tobacco use within the last 30 days.