IMT Therapy for Pompe Disease

Overseen By Maria Manson

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Copd, Significant mental illness, Dementia, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 26 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inspiratory muscle training (IMT) method for individuals with Late-onset Pompe Disease (LOPD), a condition affecting muscles and movement. Researchers aim to determine if a high-dose IMT, conducted remotely via a mobile device, is safe and beneficial for breathing and overall well-being. Participants will use the Pr02 mobile device, an oxygen therapy device, three times a week for 26 weeks. The trial suits adults with a confirmed LOPD diagnosis who have maintained stable treatment for over six months and have access to a computer and smartphone. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance the quality of life for LOPD patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be stable on your current Pompe disease treatment regimen for more than 6 months to participate.

What prior data suggests that this device is safe for use in Late-onset Pompe Disease?

Research shows that specific safety information for the Pr02 mobile device used in Inspiratory Muscle Training (IMT) for people with Pompe Disease is not yet available. Detailed safety results have not been published or are still under study.

The trial is labeled "Not Applicable," indicating it might be in the early research stages. Early trials often focus on determining a treatment's safety for participants. Although specific safety data for this device is lacking, researchers conduct early trials with caution and close monitoring.

The Pr02 mobile device guides breathing exercises, which are generally considered safe. However, without specific data, discussing potential risks and benefits with the study team and your doctor is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard enzyme replacement therapy for Pompe Disease, the Pr02 mobile device focuses on Inspiratory Muscle Training (IMT) to strengthen breathing muscles. Most current treatments aim to replace the missing enzyme causing the disease, but this approach targets muscle function directly. Researchers are excited because IMT could enhance respiratory efficiency and quality of life, offering a complementary strategy to existing therapies and potentially reducing the need for ventilatory support.

What evidence suggests that this inspiratory muscle training is effective for Late-onset Pompe Disease?

Research has shown that inspiratory muscle training (IMT) strengthens breathing muscles, aiding those with respiratory issues. IMT targets the muscles involved in breathing. In past studies, patients who regularly practiced IMT experienced improved breathing and found daily activities easier. This trial will provide participants with high-dose IMT to assess its effectiveness specifically for individuals with Late-onset Pompe Disease (LOPD). While specific data on high-dose IMT for LOPD is limited, the general benefits of muscle training for breathing are promising. This treatment aims to enhance breathing by fortifying the muscles used for respiration, which is crucial for people with LOPD. ^{4 6 7 8 9}

Who Is on the Research Team?

Harrison Jones, PhD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults diagnosed with Late-onset Pompe Disease (LOPD) who have been stable on their current treatment for over six months can join. They must be able to follow study instructions, have a minimum inspiratory muscle strength, and access to technology for remote participation. Those with severe lung diseases, significant mental illness, dementia or prior gene therapy for LOPD cannot participate.

Inclusion Criteria

Access to computer and smartphone/tablet with reliable internet connection for video visits and sensor-based respiratory technologies

I have been on the same Pompe disease treatment for over 6 months.

I have been diagnosed with Late-Onset Pompe Disease (LOPD).

Exclusion Criteria

I am unable to understand and give consent for medical procedures.

Inability to read and understand English

I have had gene therapy for Pompe disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo high-dose inspiratory muscle training (IMT) 3 times a week over 26 weeks

26 weeks

Remote sessions

Follow-up

Participants are monitored for changes in respiratory and patient-reported outcomes

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pr02 mobile device

Trial Overview The trial is testing high-dose inspiratory muscle training (IMT) using the Pr02 mobile device in people with LOPD. It's done remotely and aims to check if it's safe and doable while measuring its impact on breathing function and patient-reported outcomes.

How Is the Trial Designed?

Group I: High Dose Inspiratory Muscle Training Experimental Treatment 1 Intervention

Inspiratory Muscle Training 3 times a week over 26 weeks

Pr02 mobile device is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Portable Oxygen Concentrator for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Pulmonary Fibrosis
• Cystic Fibrosis
• Late-onset Pompe Disease (LOPD)

Approved in European Union as Portable Oxygen Concentrator for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Pulmonary Fibrosis
• Cystic Fibrosis
• Late-onset Pompe Disease (LOPD)

Approved in Canada as Portable Oxygen Concentrator for:

• Chronic Obstructive Pulmonary Disease (COPD)
• Pulmonary Fibrosis
• Cystic Fibrosis
• Late-onset Pompe Disease (LOPD)

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Genzyme, a Sanofi Company

Industry Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

Published Research Related to This Trial

In a case study of a CRIM-positive infant with Pompe disease, immune modulation therapy (IMT) allowed for the safe reintroduction of enzyme replacement therapy (ERT) after initial complications due to high antibody levels against the treatment.

While the patient did not show improvements in motor skills and remained ventilator-dependent, the use of IMT led to the disappearance of antibodies and improvement in cardiomyopathy, suggesting potential benefits in managing similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Modulation Therapy in a CRIM-Positive and IgG Antibody-Positive Infant with Pompe Disease Treated with Alglucosidase Alfa: A Case Report. Markic, J., Polic, B., Kuzmanic-Samija, R., et al.[2021]

The immune tolerance induction (ITI) regimen, combined with enzyme replacement therapy (ERT), was safely administered to seven CRIM-negative infantile Pompe disease patients, showing promise in improving clinical outcomes compared to ERT alone.

Patients on the ITI regimen had significantly lower antibody titers and four remained antibody-free, suggesting that early identification and treatment can enhance the efficacy of ERT in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT. Banugaria, SG., Prater, SN., Patel, TT., et al.[2021]

In a study of 97 patients with neuromyelitis optica spectrum disorder (NMOSD) over 8 years, intravenous methylprednisolone (IVMP) was the primary treatment for acute attacks, with 36.7% of patients experiencing adverse events, the most common being hyperglycemia.

Plasma exchange (PLEX), used for patients not responding to IVMP, had a higher adverse event rate of 61.1%, with hypocalcemia being the most frequent issue, indicating that while both treatments are effective, PLEX carries a greater risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective study of the adverse events of the treatment for an acute attack of neuromyelitis optica spectrum disorder. Veerachit-O-Larn, T., Siritho, S., Prayoonwiwat, N.[2021]

In a study involving 20 NMOSD patients, the combination of intravenous methylprednisolone (IVMT) and intravenous immunoglobulin (IVIg) significantly improved neurological function at discharge compared to IVMT alone.

Patients receiving IVMT + IVIg experienced a longer time to the next relapse (17.39 months) compared to those on IVMT alone (9.50 months), particularly benefiting relapsed patients and those who were AQP4-antibody positive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin as the rescue treatment in NMOSD patients. Lin, J., Xue, B., Zhu, R., et al.[2021]

Home infusion therapy for Pompe disease is feasible under certain conditions, allowing patients to receive enzyme replacement therapy (ERT) in a more comfortable setting, but decisions must be made on an individual basis.

The implementation of home infusion requires specially trained nursing staff, and while it can reduce patient stress, it also carries risks such as allergic reactions, necessitating proper medical oversight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. Hahn, A., Lampe, C., Boentert, M., et al.[2021]

Home infusion therapy for Pompe disease is feasible under certain conditions, allowing patients to receive enzyme replacement therapy (ERT) in a more comfortable setting, but decisions must be made on an individual basis.

The implementation of home infusion requires specially trained nursing staff, and while it can reduce patient stress, it also carries risks such as allergic reactions, necessitating proper medical oversight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. Hahn, A., Lampe, C., Boentert, M., et al.[2021]

In a case study of a CRIM-positive infant with Pompe disease, an immune modulation therapy (IMT) protocol allowed for the safe reintroduction of enzyme replacement therapy (ERT) after severe infusion reactions, leading to undetectable antibody levels and improved cardiomyopathy.

Despite the treatment, the patient remained ventilator-dependent and did not show gains in motor skills, indicating that while IMT was effective in managing antibody levels and improving heart function, it did not fully reverse the clinical decline associated with Pompe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of immune modulation therapy in the first Croatian infant diagnosed with Pompe disease: a 3-year follow-up study. Markic, J., Polic, B., Stricevic, L., et al.[2022]

In a study of 53 patients with neuromyelitis optica spectrum disorder (NMOSD), 16 patients contracted COVID-19, with a case fatality ratio of 6.25%, highlighting the potential severity of COVID-19 in this population.

The COVID-19 vaccines showed a favorable safety profile, with only mild adverse effects reported (pain at the injection site) among the 9 patients who were vaccinated, suggesting that vaccination is safe for NMOSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COVID-19 and vaccination against SARS-CoV-2 in patients with neuromyelitis optica spectrum disorders. Jovicevic, V., Ivanovic, J., Andabaka, M., et al.[2022]

Disease-modifying treatments (DMTs) for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) can lead to infections, which are the most common adverse events associated with these therapies.

An international workshop highlighted the need for tailored risk mitigation strategies for specific populations, such as children and pregnant women, and emphasized the importance of understanding DMT-related infection risks, especially in the context of the ongoing SARS-CoV-2 pandemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021. Tur, C., Dubessy, AL., Otero-Romero, S., et al.[2022]

Therapeutic plasma exchange (TPE) significantly improves recovery outcomes in patients with neuromyelitis optica spectrum disorders (NMOSD) when used alongside high-dose steroids, increasing the likelihood of returning to baseline disability status at discharge and follow-up.

In a systematic review of 1211 attacks involving 433 patients, TPE was associated with better visual acuity outcomes compared to high-dose steroids alone, suggesting it may enhance recovery during acute NMOSD attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic plasma exchange vs conventional treatment with intravenous high dose steroid for neuromyelitis optica spectrum disorders (NMOSD): a systematic review and meta-analysis. Siritho, S., Nopsopon, T., Pongpirul, K.[2021]

Initiating enzyme replacement therapy (ERT) for infantile-onset Pompe disease (IOPD) within the first 10 days of life led to significantly better clinical outcomes, including normal heart size and near-normal motor and cognitive functions, in a study of 26 treated patients over an average follow-up of 6.18 years.

The study's rapid diagnostic and treatment strategy resulted in superior outcomes compared to other medical centers, highlighting the importance of early intervention in managing IOPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme. Yang, CF., Liao, TE., Chu, YL., et al.[2023]

Enzyme replacement therapy (ERT) significantly reduces the risk of wheelchair dependency in adult patients with Pompe disease, with a hazard ratio of 0.36 based on a study of 189 patients over a median follow-up of 5 years.

However, ERT did not show a significant effect on the risk of needing respiratory support, indicating that while it helps with mobility, it may not impact respiratory function in the same way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy reduces the risk for wheelchair dependency in adult Pompe patients. van der Meijden, JC., Kruijshaar, ME., Rizopoulos, D., et al.[2019]

An 8-week inspiratory muscle training (IMT) program significantly improved maximum inspiratory pressure in eight patients with late-onset Pompe disease (LOPD) receiving enzyme replacement therapy, indicating enhanced respiratory muscle strength.

While IMT positively affected inspiratory pressure, it did not lead to significant changes in other pulmonary function tests, quality of life scores (except for social isolation), or sleep quality, suggesting that IMT may specifically target inspiratory muscle function without broadly impacting overall health metrics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inspiratory Muscle Training in Late-Onset Pompe Disease: The Effects on Pulmonary Function Tests, Quality of Life, and Sleep Quality. Aslan, GK., Huseyinsinoglu, BE., Oflazer, P., et al.[2018]

In a study of 28 infants with infantile-onset Pompe disease (IOPD) treated with high-dose enzyme replacement therapy (ERT), those who started treatment earlier had better motor outcomes, with significant differences in gross motor decline based on the timing of ERT initiation.

Lower levels of serum creatine kinase (CK) and urinary glucose tetrasaccharide (uGlc4) were associated with better responses to ERT, suggesting that monitoring these biomarkers can help optimize treatment strategies for IOPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences. Chien, YH., Tsai, WH., Chang, CL., et al.[2022]

A retrospective study involving 28 patients with Infantile Onset Pompe Disease (IOPD) showed that enzyme replacement therapy (ERT) significantly improves survival and outcomes, particularly in patients with a positive cross-reactive immunological status (CRIM-positive).

Despite the benefits of ERT, the study revealed that the treatment does not fully stabilize or reverse disease progression, as evidenced by a slow decline in motor and respiratory functions in some patients, highlighting the need for further research and new treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. Parini, R., De Lorenzo, P., Dardis, A., et al.[2019]

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