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

29 Participants Needed

Trial Summary

What is the purpose of this trial?

Study Objectives: 1) assess the safety and feasibility of high-dose inspiratory muscle training (IMT) delivered remotely in Late-onset Pompe Disease (LOPD) and 2) determine its effects on respiratory and patient-reported outcomes.

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 data supports the idea that IMT Therapy for Pompe Disease is an effective treatment?

The available research shows that Inspiratory Muscle Training (IMT) can be beneficial for people with Late-Onset Pompe Disease (LOPD). In a study, eight patients who did IMT for eight weeks experienced improvements in their lung function, quality of life, and sleep quality. This suggests that IMT can help strengthen the muscles used for breathing, which is important for people with LOPD. While other treatments like enzyme replacement therapy (ERT) are also used for Pompe Disease, IMT specifically targets breathing muscles and can be a helpful addition to ERT. ^{1 2 3 4 5}

What safety data exists for IMT Therapy for Pompe Disease?

The provided research does not contain any safety data related to IMT Therapy for Pompe Disease or its alternative names such as Pr02 mobile device, Portable Oxygen Concentrator, or Oxygen Therapy Device. The studies focus on treatments for neuromyelitis optica spectrum disorder (NMOSD) and do not mention Pompe Disease or the specified therapy. ^{6 7 8 9 10}

Is the Pr02 mobile device a promising treatment for Pompe Disease?

The provided research articles do not mention the Pr02 mobile device or its effectiveness for treating Pompe Disease. They focus on immune modulation therapy and enzyme replacement therapy, which are different treatments for the disease. ^{11 12 13 14 15}

Research Team

Harrison Jones, PhD

Principal Investigator

Duke University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

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 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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. [2019]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy reduces the risk for wheelchair dependency in adult Pompe patients. [2019]

5. United States 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. [2018]

6. Australia pubmed.ncbi.nlm.nih.gov

Retrospective study of the adverse events of the treatment for an acute attack of neuromyelitis optica spectrum disorder. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

COVID-19 and vaccination against SARS-CoV-2 in patients with neuromyelitis optica spectrum disorders. [2022]

8. England 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. [2022]

9. Germany 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. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin as the rescue treatment in NMOSD patients. [2021]

11. Austria 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. [2022]

12. United States 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. [2021]

13. United States 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. [2021]

14. Germany pubmed.ncbi.nlm.nih.gov

[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. [2021]

15. Germany pubmed.ncbi.nlm.nih.gov

[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. [2021]