Mechanical Insufflation for ALS

(MI-PALS Trial)

Overseen By Jason Ackrivo, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Pennsylvania

Disqualifiers: Emphysema, COPD, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Mechanical Insufflation-Exsufflation (MI-E) for ALS?

Research shows that Mechanical Insufflation-Exsufflation (MI-E) can help clear airways in patients with ALS by generating effective cough flows, especially in those without severe bulbar dysfunction (problems with the muscles used for speaking and swallowing). Additionally, combining MI-E with high-frequency oscillations may improve its effectiveness in managing respiratory secretions. ^{1 2 3 4 5}

Is mechanical insufflation-exsufflation (MI-E) safe for use in humans?

Research on mechanical insufflation-exsufflation (MI-E) in patients with conditions like ALS and neuromuscular diseases suggests it is generally safe, as studies focus on its effectiveness and physiological benefits without highlighting significant safety concerns. ^{1 2 3 4 5}

How is the Mechanical Insufflation-Exsufflation (MI-E) treatment unique for ALS?

The Mechanical Insufflation-Exsufflation (MI-E) treatment is unique for ALS as it helps manage respiratory secretions noninvasively by simulating a natural cough, which is crucial for patients with weakened respiratory muscles. This treatment can be enhanced with high-frequency oscillations to improve cough effectiveness, especially in patients with bulbar dysfunction, which affects the throat and mouth muscles. ^{1 3 5 6 7}

What is the purpose of this trial?

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.

Research Team

Jason Ackrivo, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults over 18 with early-stage amyotrophic lateral sclerosis (ALS) who have a caregiver to help them. Participants must be non-smokers, not using mechanical insufflation-exsufflation (MI-E), and without certain respiratory or heart conditions. Pregnant individuals or those on specific ventilation treatments are excluded.

Inclusion Criteria

I have someone to help me with my daily medical device use.

I am willing and able to follow the study's procedures.

I have been diagnosed with ALS.

Exclusion Criteria

I am using a cough assist device for airway clearance.

You currently have a tracheostomy.

I have a history of chronic obstructive pulmonary disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants perform mechanical insufflation using the BiWaze Cough system for mucus clearance, with 5 sets of 5 insufflations twice daily

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Monitoring of tracheostomy-free survival time and time to start of non-invasive ventilation

1 year

Treatment Details

Interventions

• Mechanical Insufflation

Trial Overview The study tests the effects of mechanical insufflation using the BiWaze Cough system on breathing in ALS patients. It's a single-arm study comparing peak cough flow in participants using MI daily against those who do not use it.

Participant Groups

Group I: Mechanical insufflation Experimental Treatment 1 Intervention

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

Mechanical Insufflation is already approved in United States, European Union for the following indications:

Approved in United States as Mechanical Insufflation-Exsufflation (MI-E) for:

• Amyotrophic lateral sclerosis (ALS)
• Mucus clearance

Approved in European Union as Mechanical Insufflation-Exsufflation (MI-E) for:

• Amyotrophic lateral sclerosis (ALS)
• Neuromuscular disorders
• Mucus clearance

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

In a study of 69 ALS patients, mechanical assisted coughing with insufflation-exsufflation (MI-E) was effective in detecting airway obstruction and optimizing treatment parameters, achieving effective MI-E in 98.55% of subjects after adjustments.

The study found that bulbar upper motor neuron dysfunction was linked to airway obstruction during insufflation, while bulbar lower motor neuron dysfunction was associated with upper-airway collapse during exsufflation, highlighting the importance of assessing bulbar function in ALS patients for effective MI-E.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Waveforms Analysis in Patients With Amyotrophic Lateral Sclerosis for Enhanced Efficacy of Mechanically Assisted Coughing. Sancho, J., Ferrer, S., Bures, E., et al.[2023]

Mechanical insufflation-exsufflation (MI-E) can effectively generate clinically useful expiratory flows (> 2.7 L/s) in stable ALS patients, but this is not the case for those with severe bulbar dysfunction and specific lung function parameters.

Patients with bulbar dysfunction who have a maximum insufflation capacity (MIC) greater than 1 L and a peak cough flow (PCF) from maximum insufflation (PCFMIC) less than 2.7 L/s may experience ineffective MI-E due to severe airway collapse during exsufflation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis. Sancho, J., Servera, E., Díaz, J., et al.[2022]

In a study of 20 ALS patients and 20 healthy volunteers, it was found that patients with bulbar symptoms exhibited abnormal laryngeal movements during mechanical insufflation-exsufflation (MI-E), which compromised their ability to cough effectively.

Customizing MI-E settings for individual patients, especially those with bulbar symptoms, could enhance the effectiveness of this non-invasive treatment by addressing the observed laryngeal adduction that limits airway size during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis. Andersen, T., Sandnes, A., Brekka, AK., et al.[2018]

Mechanical insufflation-exsufflation (MI-E) is well-tolerated by children with neuromuscular diseases, showing significant improvements in respiratory comfort and airflow without adverse effects on breathing patterns or oxygen saturation.

The application of MI-E at higher pressures (up to 40 cm H(2)O) resulted in a substantial increase in expired volume and improved peak expiratory flow, indicating its efficacy in enhancing respiratory function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic benefits of mechanical insufflation-exsufflation in children with neuromuscular diseases. Fauroux, B., Guillemot, N., Aubertin, G., et al.[2008]

In a study involving 47 medically stable ALS patients, the addition of high-frequency oscillations (HFO) to mechanically assisted coughing (MI-E) did not improve the cough peak flow compared to MI-E alone.

The study measured cough peak flow under four different conditions, and results showed no significant differences, indicating that HFO may not enhance the effectiveness of MI-E in managing respiratory secretions in ALS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of High-Frequency Oscillations on Cough Peak Flows Generated by Mechanical In-Exsufflation in Medically Stable Subjects With Amyotrophic Lateral Sclerosis. Sancho, J., Bures, E., de La Asunción, S., et al.[2019]

In a study using a mechanical lung model to simulate infants with tracheostomy tubes, it was found that an insufflation time of more than 1 second is necessary for proper pressure equilibration, which is crucial for effective cough augmentation using the mechanical in-exsufflator (MIE).

The research demonstrated that while higher insufflation pressures can increase lung volumes and expiratory flow rates, the most significant improvement in maximal expiratory flow (MEF) was achieved with more negative exsufflation pressures, highlighting the importance of both parameters in optimizing MIE use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of a lung model to assess mechanical in-exsufflator therapy in infants with tracheostomy. Striegl, AM., Redding, GJ., Diblasi, R., et al.[2013]

In a 2-year study involving 19 ALS patients, adding oscillations to mechanical insufflation-exsufflation (MI-E) did not significantly reduce the rate of respiratory infections compared to conventional MI-E.

The study found no difference in the need for hospital admissions or bronchoscopy procedures between the two treatment methods, indicating that oscillations may not provide additional benefits in managing respiratory secretions in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical Insufflation-Exsufflation With Oscillations in Amyotrophic Lateral Sclerosis With Home Ventilation via Tracheostomy. Sancho, J., Burés, E., Ferrer, S., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Waveforms Analysis in Patients With Amyotrophic Lateral Sclerosis for Enhanced Efficacy of Mechanically Assisted Coughing. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Physiologic benefits of mechanical insufflation-exsufflation in children with neuromuscular diseases. [2008]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of High-Frequency Oscillations on Cough Peak Flows Generated by Mechanical In-Exsufflation in Medically Stable Subjects With Amyotrophic Lateral Sclerosis. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Use of a lung model to assess mechanical in-exsufflator therapy in infants with tracheostomy. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Mechanical Insufflation-Exsufflation With Oscillations in Amyotrophic Lateral Sclerosis With Home Ventilation via Tracheostomy. [2023]