Pompe DiseaseNCT07664930
Phrenic Nerve and Diaphragm Electrophysiology in Pompe Disease
An observational study of Pompe Disease, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
Trial summary
Pompe disease is traditionally considered a lysosomal myopathy. However, increasing experimental and clinical evidence suggests involvement of the entire motor unit, including motor neurons, peripheral nerves, neuromuscular junctions, and skeletal muscle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pompe Disease
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 30 Mar 2026to 28 Feb 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
Study population: Approximately 20 adult patients with genetically confirmed Pompe disease are expected to be prospectively included. In addition, a retrospective review of approximately 150 previously performed phrenic nerve conduction studies and diaphragm electromyography examinations in patients with unexplained respiratory failure will be conducted. The prospective enrollment refers exclusively to newly evaluated Pompe disease patients, while the retrospective component is based on existing clinical records and neurophysiological data
Who may be able to join
- Age ≥ 18 years.
- For the prospective cohort:
- Genetically confirmed diagnosis of Pompe disease.
- Ability to undergo routine neurophysiological and respiratory assessments.
- Written informed consent provided.
- For the retrospective cohort:
- History of restrictive respiratory failure or unexplained hypoventilation.
- Availability of previous phrenic nerve conduction studies and/or diaphragm electromyography performed as part of routine clinical evaluation.
Who cannot join
- Age < 18 years.
- For the prospective cohort:
- Conditions preventing completion of neurophysiological assessments (e.g., inability to maintain required positioning or relevant clinical contraindications).
- Known primary phrenic nerve injury (e.g., postsurgical phrenic palsy or documented traumatic phrenic neuropathy).
- Presence of other neuromuscular disorders potentially confounding data interpretation.
- Refusal or inability to provide informed consent.
Show all 10Show fewer
- For the retrospective cohort:
- Incomplete or technically non-interpretable neurophysiological examinations.
- Previously established respiratory or neuromuscular diagnoses fully explaining respiratory impairment.
- Cases requiring additional clinical information for study purposes when patient consent for contact or data completion cannot be obtained.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Translational Neurophysiology
Pavia, 27100
Giuseppe Cosentino, MD, 0382380249 ext. 0039, giuseppe.cosentino@mondino.it
Cinzia Fattore, MD, 0382380385 ext. 0039, cinzia.fattore@unipv.it
About this study
Official title: Electrophysiological Study of the Phrenic Nerve and Diaphragm in Pompe Disease: Retrospective and Prospective Cohort Analysis
Pompe disease is traditionally considered a lysosomal myopathy. However, increasing experimental and clinical evidence suggests involvement of the entire motor unit, including motor neurons, peripheral nerves, neuromuscular junctions, and skeletal muscle. Respiratory impairment is a major cause of morbidity and mortality, and diaphragm dysfunction is frequently observed.
Clinical observations at IRCCS Fondazione Mondino have highlighted neurophysiological abnormalities of the phrenic nerve and diaphragm in patients with Pompe disease and respiratory involvement, sometimes occurring even in the absence of clinically significant limb muscle weakness. These findings suggest that respiratory motor unit dysfunction may represent an important component of the disease phenotype.
This observational study aims to systematically characterize phrenic nerve conduction parameters and diaphragm electromyographic findings in adult patients with genetically confirmed Pompe disease and in patients with unexplained respiratory failure. Retrospective and prospective clinical, neurophysiological, and respiratory data collected during routine clinical care will be analyzed to explore whether phrenic nerve and diaphragm abnormalities may serve as markers of respiratory motor unit involvement in Pompe disease.
Read the detailed description
This is a non-interventional observational study with a mixed retrospective and prospective cohort design. No experimental treatments, additional diagnostic procedures, or study-specific interventions are introduced. All data derive exclusively from routine clinical evaluations performed as part of standard patient care. Two main populations are included: 1) Adult patients with genetically confirmed Pompe disease undergoing routine neurophysiological and respiratory assessments; 2) Patients with restrictive respiratory failure or unexplained hypoventilation who previously underwent phrenic nerve conduction studies and/or diaphragm electromyography as part of clinical workup, identified retrospectively. The retrospective component consists of systematic review of phrenic nerve conduction studies and diaphragm electromyography performed over previous years in patients with suspected neuromuscular respiratory failure. The prospective component involves standardized collection of neurophysiological and respiratory data obtained during routine follow-up of patients with confirmed Pompe disease.
Neurophysiological assessments include bilateral phrenic nerve motor conduction studies and evaluation of peripheral nerves and limb muscles. Diaphragm needle electromyography is performed only when clinically indicated. Respiratory evaluations include spirometry with forced vital capacity in seated and supine positions, maximal inspiratory and expiratory pressures (MIP/MEP), and, when clinically required, overnight ventilation studies.
The primary outcome is the characterization of phrenic nerve conduction parameters, including motor latency, compound muscle action potential amplitude, and presence or absence of diaphragmatic responses. Secondary outcomes include diaphragm electromyographic patterns, comparison between phrenic nerve and other peripheral nerves, and correlations between neurophysiological parameters and respiratory function.
Data are collected retrospectively from medical records and prospectively during routine clinical visits, pseudonymized, and analyzed descriptively and exploratorily. The study aims to improve characterization of respiratory motor unit involvement in Pompe disease and to evaluate the potential diagnostic contribution of phrenic nerve and diaphragm electrophysiology in patients with unexplained respiratory failure.
- Conditions
- Pompe Disease
- Keywords
- Pompe disease, Phrenic nerve, Diaphragm, Respiratory muscle weakness, Neuromuscular respiratory failure, Motor unit
- Medical subject headings
- Glycogen Storage Disease Type II
What is being measured
The primary outcome is the main question the study is designed to answer.
Motor latency (ms)
Phrenic nerve conduction parameter measured by bilateral nerve conduction studies
Measured: Baseline (at first available assessment, retrospective or prospective)
Compound muscle action potential (CMAP) amplitude (millivolts)
Phrenic nerve conduction parameter assessed bilaterally by nerve conduction studies
Measured: Baseline (at first available assessment, retrospective or prospective)
Presence or absence of diaphragmatic responses
Phrenic nerve conduction parameter assessed bilaterally
Measured: Baseline (at first available assessment, retrospective or prospective)
Secondary outcomes (4)
Neurogenic pattern
Diaphragm electromyography pattern assessed when clinically indicated
Measured: Baseline (at time of clinical assessment when EMG is performed)
Myopathic pattern
Diaphragm electromyography pattern assessed when clinically indicated
Measured: Baseline (at time of clinical assessment when EMG is performed)
Mixed pattern
Diaphragm electromyography pattern assessed when clinically indicated
Measured: Baseline (at time of clinical assessment when EMG is performed)
Normal pattern
Diaphragm electromyography pattern assessed when clinically indicated
Measured: Baseline (at time of clinical assessment when EMG is performed)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2026
- Study start30 Mar 2026
- Primary completion28 Feb 2029 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Pompe DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Fondazione Salvatore Maugeri
- Responsible party
- Sponsor
- Investigators
- Giuseppe Cosentino, MD, Principal investigator, Translational Neurophysiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07664930
- Sponsor's protocol ID
- POMPE-PHRENIC
- Status last verified
- Apr 2026
- First submitted
- 20 Apr 2026
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
DeRuisseau LR, Fuller DD, Qiu K, DeRuisseau KC, Donnelly WH Jr, Mah C, Reier PJ, Byrne BJ. Neural deficits contribute to respiratory insufficiency in Pompe disease. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9419-24. doi: 10.1073/pnas.0902534106. Epub 2009 May 27.
PubMed 19474295Falk DJ, Todd AG, Lee S, Soustek MS, ElMallah MK, Fuller DD, Notterpek L, Byrne BJ. Peripheral nerve and neuromuscular junction pathology in Pompe disease. Hum Mol Genet. 2015 Feb 1;24(3):625-36. doi: 10.1093/hmg/ddu476. Epub 2014 Sep 12.
PubMed 25217571ElMallah MK, Pagliardini S, Turner SM, Cerreta AJ, Falk DJ, Byrne BJ, Greer JJ, Fuller DD. Stimulation of Respiratory Motor Output and Ventilation in a Murine Model of Pompe Disease by Ampakines. Am J Respir Cell Mol Biol. 2015 Sep;53(3):326-35. doi: 10.1165/rcmb.2014-0374OC.
PubMed 25569118Turner SMF, Falk DJ, Byrne BJ, Fuller DD. Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates widespread neuropathology. Physiol Genomics. 2016 Nov 1;48(11):785-794. doi: 10.1152/physiolgenomics.00075.2016. Epub 2016 Sep 9.
PubMed 27614205Oliveira Santos M, Domingues S, de Campos CF, Moreira S, de Carvalho M. Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration. J Neurol Sci. 2024 May 15;460:123021. doi: 10.1016/j.jns.2024.123021. Epub 2024 Apr 18.
PubMed 38653115Spiesshoefer J, Henke C, Kabitz HJ, Brix T, Gorlich D, Herkenrath S, Randerath W, Young P, Boentert M. The nature of respiratory muscle weakness in patients with late-onset Pompe disease. Neuromuscul Disord. 2019 Aug;29(8):618-627. doi: 10.1016/j.nmd.2019.06.011. Epub 2019 Jun 22.
PubMed 31327549
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiological Study of the Phrenic Nerve and Diaphragm in Pompe Disease: Retrospective and Prospective Cohort Analysis
- ClinicalTrials.gov ID
- NCT07664930
- Acronym / sponsor ID
- POMPE-PHRENIC
- Conditions
- Pompe Disease
- Keywords
- Pompe disease, Phrenic nerve, Diaphragm, Respiratory muscle weakness, Neuromuscular respiratory failure, Motor unit
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- IRCCS National Neurological Institute "C. Mondino" FoundationUniversity, hospital or other
- Collaborators
- Fondazione Salvatore Maugeri
- Study start
- 30 Mar 2026 (actual)
- Primary completion
- 28 Feb 2029 (estimated)
- Study completion
- 28 Feb 2029 (estimated)
- First posted
- 24 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pompe disease is traditionally considered a lysosomal myopathy. However, increasing experimental and clinical evidence suggests involvement of the entire motor unit, including motor neurons, peripheral nerves, neuromuscular junctions, and skeletal muscle. Respiratory impairment is a major cause of morbidity and mortality, and diaphragm dysfunction is frequently observed.
Clinical observations at IRCCS Fondazione Mondino have highlighted neurophysiological abnormalities of the phrenic nerve and diaphragm in patients with Pompe disease and respiratory involvement, sometimes occurring even in the absence of clinically significant limb muscle weakness. These findings suggest that respiratory motor unit dysfunction may represent an important component of the disease phenotype.
This observational study aims to systematically characterize phrenic nerve conduction parameters and diaphragm electromyographic findings in adult patients with genetically confirmed Pompe disease and in patients with unexplained respiratory failure. Retrospective and prospective clinical, neurophysiological, and respiratory data collected during routine clinical care will be analyzed to explore whether phrenic nerve and diaphragm abnormalities may serve as markers of respiratory motor unit involvement in Pompe disease.
Detailed description
This is a non-interventional observational study with a mixed retrospective and prospective cohort design. No experimental treatments, additional diagnostic procedures, or study-specific interventions are introduced. All data derive exclusively from routine clinical evaluations performed as part of standard patient care. Two main populations are included: 1) Adult patients with genetically confirmed Pompe disease undergoing routine neurophysiological and respiratory assessments; 2) Patients with restrictive respiratory failure or unexplained hypoventilation who previously underwent phrenic nerve conduction studies and/or diaphragm electromyography as part of clinical workup, identified retrospectively. The retrospective component consists of systematic review of phrenic nerve conduction studies and diaphragm electromyography performed over previous years in patients with suspected neuromuscular respiratory failure. The prospective component involves standardized collection of neurophysiological and respiratory data obtained during routine follow-up of patients with confirmed Pompe disease.
Neurophysiological assessments include bilateral phrenic nerve motor conduction studies and evaluation of peripheral nerves and limb muscles. Diaphragm needle electromyography is performed only when clinically indicated. Respiratory evaluations include spirometry with forced vital capacity in seated and supine positions, maximal inspiratory and expiratory pressures (MIP/MEP), and, when clinically required, overnight ventilation studies.
The primary outcome is the characterization of phrenic nerve conduction parameters, including motor latency, compound muscle action potential amplitude, and presence or absence of diaphragmatic responses. Secondary outcomes include diaphragm electromyographic patterns, comparison between phrenic nerve and other peripheral nerves, and correlations between neurophysiological parameters and respiratory function.
Data are collected retrospectively from medical records and prospectively during routine clinical visits, pseudonymized, and analyzed descriptively and exploratorily. The study aims to improve characterization of respiratory motor unit involvement in Pompe disease and to evaluate the potential diagnostic contribution of phrenic nerve and diaphragm electrophysiology in patients with unexplained respiratory failure.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Approximately 20 adult patients with genetically confirmed Pompe disease are expected to be prospectively included. In addition, a retrospective review of approximately 150 previously performed phrenic nerve conduction studies and diaphragm electromyography examinations in patients with unexplained respiratory failure will be conducted. The prospective enrollment refers exclusively to newly evaluated Pompe disease patients, while the retrospective component is based on existing clinical records and neurophysiological data
Key inclusion criteria (8 listed)
- Age ≥ 18 years.
- Genetically confirmed diagnosis of Pompe disease.
- Ability to undergo routine neurophysiological and respiratory assessments.
- Written informed consent provided.
- History of restrictive respiratory failure or unexplained hypoventilation.
Key exclusion criteria (10 listed)
- Age < 18 years.
- Conditions preventing completion of neurophysiological assessments (e.g., inability to maintain required positioning or relevant clinical contraindications).
- Known primary phrenic nerve injury (e.g., postsurgical phrenic palsy or documented traumatic phrenic neuropathy).
- Presence of other neuromuscular disorders potentially confounding data interpretation.
- Refusal or inability to provide informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Motor latency (ms)
Time frame: Baseline (at first available assessment, retrospective or prospective)
Phrenic nerve conduction parameter measured by bilateral nerve conduction studies
Compound muscle action potential (CMAP) amplitude (millivolts)
Time frame: Baseline (at first available assessment, retrospective or prospective)
Phrenic nerve conduction parameter assessed bilaterally by nerve conduction studies
Presence or absence of diaphragmatic responses
Time frame: Baseline (at first available assessment, retrospective or prospective)
Phrenic nerve conduction parameter assessed bilaterally
4 secondary outcomes
Neurogenic pattern
Time frame: Baseline (at time of clinical assessment when EMG is performed)
Myopathic pattern
Time frame: Baseline (at time of clinical assessment when EMG is performed)
Mixed pattern
Time frame: Baseline (at time of clinical assessment when EMG is performed)
Normal pattern
Time frame: Baseline (at time of clinical assessment when EMG is performed)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Background: PubMed 19474295DeRuisseau LR, Fuller DD, Qiu K, DeRuisseau KC, Donnelly WH Jr, Mah C, Reier PJ, Byrne BJ. Neural deficits contribute to respiratory insufficiency in Pompe disease. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9419-24. doi: 10.1073/pnas.0902534106. Epub 2009 May 27.
- Background: PubMed 25217571Falk DJ, Todd AG, Lee S, Soustek MS, ElMallah MK, Fuller DD, Notterpek L, Byrne BJ. Peripheral nerve and neuromuscular junction pathology in Pompe disease. Hum Mol Genet. 2015 Feb 1;24(3):625-36. doi: 10.1093/hmg/ddu476. Epub 2014 Sep 12.
- Background: PubMed 25569118ElMallah MK, Pagliardini S, Turner SM, Cerreta AJ, Falk DJ, Byrne BJ, Greer JJ, Fuller DD. Stimulation of Respiratory Motor Output and Ventilation in a Murine Model of Pompe Disease by Ampakines. Am J Respir Cell Mol Biol. 2015 Sep;53(3):326-35. doi: 10.1165/rcmb.2014-0374OC.
- Background: PubMed 27614205Turner SMF, Falk DJ, Byrne BJ, Fuller DD. Transcriptome assessment of the Pompe (Gaa-/-) mouse spinal cord indicates widespread neuropathology. Physiol Genomics. 2016 Nov 1;48(11):785-794. doi: 10.1152/physiolgenomics.00075.2016. Epub 2016 Sep 9.
- Background: PubMed 38653115Oliveira Santos M, Domingues S, de Campos CF, Moreira S, de Carvalho M. Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration. J Neurol Sci. 2024 May 15;460:123021. doi: 10.1016/j.jns.2024.123021. Epub 2024 Apr 18.
- Background: PubMed 31327549Spiesshoefer J, Henke C, Kabitz HJ, Brix T, Gorlich D, Herkenrath S, Randerath W, Young P, Boentert M. The nature of respiratory muscle weakness in patients with late-onset Pompe disease. Neuromuscul Disord. 2019 Aug;29(8):618-627. doi: 10.1016/j.nmd.2019.06.011. Epub 2019 Jun 22.
- Individual participant dataSharing planned: No
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Pompe Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuseppe Cosentino, MD principal investigator
Translational Neurophysiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pompe Disease, run by IRCCS National Neurological Institute "C. Mondino" Foundation at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuseppe Cosentino, MD (0382380249 ext. 0039, giuseppe.cosentino@mondino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Motor latency (ms) (time frame: Baseline (at first available assessment, retrospective or prospective)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07664930, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.