Mechanical Insufflation for ALS

(MI-PALS Trial)

Overseen By Kelsey Moulton

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how the BiWaze Cough device, used for mechanical insufflation to help clear mucus from the lungs, affects breathing in people with early-stage amyotrophic lateral sclerosis (ALS). Participants will use the device twice daily for six months to assess improvements in cough strength. The study will compare these results with a group not using the device. It suits those diagnosed with ALS who can perform a cough test and have a caregiver to assist with the device daily. As an unphased trial, this study offers a unique opportunity to contribute to understanding new treatment options for ALS.

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 prior data suggests that this device is safe for ALS patients?

Research shows that using a machine called mechanical insufflation-exsufflation (MI-E) is generally safe for people with ALS (amyotrophic lateral sclerosis). Studies have found that MI-E strengthens coughs, which is important for clearing mucus and keeping airways open. This is crucial for people with ALS because they often have weak coughs.

Reports suggest that most patients handle MI-E well. Experts recommend MI-E to help ALS patients with their breathing problems. While some minor discomfort, like feeling pressure during treatment, might occur, serious side effects are not commonly reported.

In summary, although MI-E may cause minor side effects, it is generally considered safe and helpful for improving breathing in people with ALS. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Mechanical insufflation for ALS is unique because it offers a non-invasive way to support breathing, especially when traditional methods like ventilators or medication can be more intrusive or less effective. Unlike other treatments that may focus on medication to manage symptoms, mechanical insufflation uses the BiWaze cough device to help clear the airway by simulating a natural cough, which could improve quality of life for patients. Researchers are excited about this method because it could potentially maintain lung function and reduce respiratory complications without the side effects associated with drugs.

What evidence suggests that mechanical insufflation is effective for ALS?

Research shows that a device called mechanical insufflation-exsufflation (MI-E), which participants in this trial will use, can help people with ALS cough more effectively by improving airway clearance. Studies have found that MI-E assists ALS patients who struggle with coughing in achieving important health goals. Using MI-E for six months might slow the decline in cough strength, measured by peak cough flow (PCF). However, some research suggests that people with mild breathing problems might not benefit from MI-E unless they experience a sudden respiratory illness. Overall, MI-E appears promising for aiding breathing in ALS, especially for those with more serious coughing difficulties. ^{1 2 6 7 8}

Who Is on the Research Team?

Jason Ackrivo, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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) 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 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]

Citations

1. nature.com nature.com/articles/s41598-025-91692-8

Provision, cough efficacy and treatment satisfaction of ... In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06119087

Study Details | NCT06119087 | Mechanical Insufflation in ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40025240/

Provision, cough efficacy and treatment satisfaction of ... In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals.

4. journal.chestnet.org journal.chestnet.org/article/S0012-3692(15)32103-6/abstract

Efficacy of Mechanical Insufflation-Exsufflation in Medically ... Clinically stable patients with mild respiratory dysfunction and PCFmic > 4 L/s might not benefit from MI-E except during an acute respiratory illness. Key ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0012369215321036

Efficacy of Mechanical Insufflation-Exsufflation in Medically ... Twenty-six consecutive patients with ALS were studied, 15 with severe bulbar dysfunction. Using a pneumotachograph and with the aid of an oronasal mask, ...

6. anthem.com anthem.com/medpolicies/abc/active/gl_pw_e003057.html

CG-DME-54 Mechanical Insufflation-Exsufflation Devices Accordingly, MI-E was cautiously recommended for children with weak cough, recommended for individuals with amyotrophic lateral sclerosis, and strongly ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6620888/

Preliminary Effectiveness and Safety of High Frequency ... Mechanical insufflation-exsufflation (MI-E) is necessary for noninvasive management of respiratory clearance in patients with neuromuscular ...

8. journal.chestnet.org journal.chestnet.org/article/S0012-3692(23)01030-9/abstract

Mechanical Insufflation-Exsufflation Implementation and ... This article will demonstrate the clinical utility of MIE graphics in titrating the initial MIE settings, guiding upper airway and lung protective strategies.