IMT Therapy for Pompe Disease
Recruiting in Palo Alto (17 mi)
Overseen ByHarrison Jones, PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Duke University
No Placebo Group
Approved in 3 jurisdictions
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.
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.
1231112What 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.
79101314What 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.
456815Do 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.
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
I am 18 years old or older.
I have been diagnosed with Late-Onset Pompe Disease (LOPD).
My lung function is more than half of what's expected for my age and sex.
Exclusion Criteria
I am unable to understand and give consent for medical procedures.
I have had gene therapy for Pompe disease.
I do not have severe COPD, significant mental illness, or dementia.
I use a machine to help me breathe when I'm awake.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: High Dose Inspiratory Muscle TrainingExperimental Treatment1 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:
πΊπΈ Approved in United States as Portable Oxygen Concentrator for:
- Chronic Obstructive Pulmonary Disease (COPD)
- Pulmonary Fibrosis
- Cystic Fibrosis
- Late-onset Pompe Disease (LOPD)
πͺπΊ Approved in European Union as Portable Oxygen Concentrator for:
- Chronic Obstructive Pulmonary Disease (COPD)
- Pulmonary Fibrosis
- Cystic Fibrosis
- Late-onset Pompe Disease (LOPD)
π¨π¦ Approved in Canada as Portable Oxygen Concentrator for:
- Chronic Obstructive Pulmonary Disease (COPD)
- Pulmonary Fibrosis
- Cystic Fibrosis
- Late-onset Pompe Disease (LOPD)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Duke University Medical CenterDurham, NC
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Who is running the clinical trial?
Duke UniversityLead Sponsor
Genzyme, a Sanofi CompanyIndustry Sponsor
References
Immune Modulation Therapy in a CRIM-Positive and IgG Antibody-Positive Infant with Pompe Disease Treated with Alglucosidase Alfa: A Case Report. [2021]Pompe disease is characterized by deficiency or absence of activity of the lysosomal enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen progressively accumulates in muscle tissues. Patients with an aggressive classic infantile-onset form generally rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alfa antibody titers and usually a poor clinical outcome of enzyme replacement therapy (ERT). CRIM-positive patients can also develop robust antibody titers complicating therapeutic management.We successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom infusions had to be temporarily discontinued because of safety concerns despite administration of pre-infusion medication. Prior to discontinuation, she had shown signs of clinical deterioration and continuous ventilation support through a tracheostomy was required. She was found to be positive for anti-alglucosidase alfa antibodies (1:6,400). IMT (rituximab, methotrexate and intravenous gamma globulin) was started, ERT was safely reintroduced during the IMT induction phase and, subsequently, the enzyme dose was increased, all without any complications. Antibodies disappeared, IMT was tapered and discontinued, and cadiomyopathy steadily improved. During 1 year of follow-up, she remained ventilator dependent and no gains in motor skills were noticed; motor functions will be closely monitored during sustained ERT.Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant with Pompe disease cannot be solely attributed to IMT, our experiences with this protocol may be helpful to other physicians encountering comparable therapeutic dilemmas.
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]Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount a strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that immune tolerance induction (ITI) prevents or diminishes the development of antibody titers, resulting in a better clinical outcome compared to CN IPD patients treated with ERT monotherapy.
Effects of immune modulation therapy in the first Croatian infant diagnosed with Pompe disease: a 3-year follow-up study. [2022]Pompe disease is a storage disorder characterized by deficient or absent activity of the enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen accumulates in muscle tissues. Patients with a classic infantile-onset form present by the first few months of life with hypertrophic cardiomyopathy and muscle weakness. If left untreated, these patients rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alpha antibody titers. However, CRIM-positive patients also sometimes develop robust antibody titers. High antibody titers complicate therapeutic management, and those patients have a worse clinical outcome of enzyme replacement therapy (ERT).Four years ago, we successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom ERT had to be discontinued because of severe infusion-associated reactions. She was found to be positive for anti-alglucosidase alpha antibodies. IMT (rituximab, methotrexate, and intravenous gammaglobulin) was started, and ERT was safely reintroduced during the IMT induction phase without any complications. Antibodies disappeared; IMT was tapered and discontinued; and cardiomyopathy steadily improved. During more than 3 years of follow-up, she remained ventilator dependent, and no gains in motor skills were noticed. The antibodies are still undetectable, and no adverse reactions associated with IMT had occurred. The cardiomyopathy is gradually increasing, but there is still ~ 50 % reduction as compared with the highest value measured. Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant cannot be solely attributed to IMT, this protocol proved itself efficient and safe.
Inspiratory Muscle Training in Late-Onset Pompe Disease: The Effects on Pulmonary Function Tests, Quality of Life, and Sleep Quality. [2018]Late-onset Pompe disease (LOPD) is characterized by progressive skeletal and respiratory muscle weakness. Little is known about the effect of inspiratory muscle training (IMT) on pulmonary function in subjects with LOPD. The aim of the present study was to investigate the effect of an 8-week IMT program on pulmonary function tests, quality of life, and sleep quality in eight patients with LOPD who were receiving enzyme replacement therapy (ERT).
Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy. [2019]Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants.
Enzyme replacement therapy reduces the risk for wheelchair dependency in adult Pompe patients. [2019]Pompe disease is a rare metabolic myopathy. In adult patients, progressive weakness of limb-girdle and respiratory muscles often leads to wheelchair and respirator dependency. Clinical studies have shown enzyme replacement therapy (ERT) to positively affect motor and respiratory outcomes. Here we investigate whether ERT reduces patients' risk of needing a wheelchair or respirator.
Retrospective study of the adverse events of the treatment for an acute attack of neuromyelitis optica spectrum disorder. [2021]Intravenous methylprednisolone (IVMP) is an initially recommended therapy for an acute attack of neuromyelitis optica spectrum disorder (NMOSD). For those who do not respond to steroid treatment, plasma exchange (PLEX) is generally added-on. We evaluated adverse events of an acute treatment in NMOSD patients in a university-based hospital during January 2009 and December 2017. Ninety-seven patients with 177 attacks were collected. The therapy included IVMP alone (123 events, 62.4%), IVMP followed by PLEX (46 events, 23.4%) and, PLEX alone (8 events, 4.5%). Adverse events occurred in 36.7% of the IVMP group and 61.1% of the PLEX group. The most common adverse event was hyperglycemia (43.5%) followed by infection (29%) in the former and hypocalcemia (63.6%) followed by hypofibrinogen (42.4%), hypotension (30.3%), and infection (21.2%) in the latter. One severe adverse event was documented in the IVMP group and 13 events in the PLEX groups, nevertheless, all were manageable.
Earlier and higher dosing of alglucosidase alfa improve outcomes in patients with infantile-onset Pompe disease: Evidence from real-world experiences. [2022]Enzyme replacement therapy (ERT), the only approved therapy for infantile-onset Pompe disease (IOPD), had heterogeneous clinical effects due to factors such as severity, age at first treatment, dosage, and dosing regimens. We report the clinical and biochemical outcomes of a cohort of IOPD patients identified through newborn screening, and evaluating the dosage effect.
Therapeutic plasma exchange vs conventional treatment with intravenous high dose steroid for neuromyelitis optica spectrum disorders (NMOSD): a systematic review and meta-analysis. [2021]Therapeutic plasma exchanges (TPE) has been recommended for neuromyelitis optica spectrum disorders (NMOSD) as a rescue therapy after nonresponding from the high-dose steroid and as an early therapy in severe attacks. We performed a systematic review to evaluate whether therapeutic plasma exchange (TPE) is better than conventional intravenous methylprednisolone (IVMP) in neuromyelitis optica spectrum disorders (NMOSD) patients.
Intravenous immunoglobulin as the rescue treatment in NMOSD patients. [2021]Intravenous immunoglobulin (IVIg) has been used for neuromyelitis optica spectrum disorder (NMOSD) patients to prevent relapses in several studies. However, efficacy of the rescue treatment of IVIG was just assessed in a small sample research. The aim of this study is to investigate the efficacy of IVIG in NMOSD as a rescue treatment and whether it could reduce the relapse rate. We retrospectively reviewed patients with NMOSD in the First and Second Affiliated Hospital of Wenzhou Medical University. Clinical parameters were extracted from the medical records, such as expanded disability scale score (EDSS) and time to next relapse. Thirty-one events of 20 NMOSD patients were included in the intravenous methylprednisolone (IVMT) + IVIG group and 72 events of 39 patients in the IVMT group. IVMT therapy combined with IVIG could improve the neurological disability when discharged (p
[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. [2021]Pompe disease is a lysosomal multisystem disorder with predominant proximal myopathy. Treatment with enzyme replacement therapy (ERT) is available requiring life-long biweekly infusions of recombinant Ξ±-glucosidase. To minimize the burden of ERT patients ask for home infusion therapy.
[Home infusion therapy for Pompe disease: Recommendations for German-speaking countries]. [2021]Pompe disease is a lysosomal multisystem disorder with predominant proximal myopathy. Treatment with enzyme replacement therapy (ERT) is available requiring life-long biweekly infusions of recombinant Ξ±-glucosidase. To minimize the burden of ERT patients ask for home infusion therapy.
COVID-19 and vaccination against SARS-CoV-2 in patients with neuromyelitis optica spectrum disorders. [2022]Reports on outcomes of COVID-19 in patients with neuromyelitis optica spectrum disorder (NMOSD) are scarce, as well as those related to the safety profile of the vaccines in this population. The aim of this survey is to present demographic and clinical characteristics of patients with NMOSD who developed COVID-19 and safety data of the COVID-19 vaccines in these persons.
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]Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.
Long-term outcomes of very early treated infantile-onset Pompe disease with short-term steroid premedication: experiences from a nationwide newborn screening programme. [2023]Starting enzyme replacement therapy (ERT) before severe irreversible muscular damage occurs is important in infantile-onset Pompe disease (IOPD). This long-term follow-up study demonstrates our diagnostic and treatment strategies for IOPD and compares our clinical outcomes with those of other medical centres.