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

April 25, 2024 updated by: University of Pennsylvania

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. Age <18 years old.
  2. Inability to perform a cough peak flow or spirometry manuever
  3. Current use of non-invasive ventilation (NIV), bi-level positive pressure ventilation, or "Bi-PAP" or physician prescribing NIV on day of potential enrollment.
  4. 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.
  5. Active enrollment in hospice.
  6. Current tracheostomy.
  7. Presence of cognitive dysfunction that would impair ability to complete study procedures, as determined by neurology attending physician.
  8. Absence of an able and willing caregiver to assist with MI twice daily as specified in the protocol.
  9. Pregnancy

  10. Medical history of any of the following:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
peak cough flow (PCF)
Time Frame: 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.
6 months

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to start of non-invasive ventilation
Time Frame: 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.
1 year
Tracheostomy free survival time
Time Frame: 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.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Investigators

  • Principal Investigator: Jason Ackrivo, MD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2024

Primary Completion (Estimated)

September 8, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 31, 2023

First Submitted That Met QC Criteria

October 31, 2023

First Posted (Actual)

November 7, 2023

Study Record Updates

Last Update Posted (Actual)

April 26, 2024

Last Update Submitted That Met QC Criteria

April 25, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 854981

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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