Phrenic Nerve and Diaphragm Electrophysiology in Pompe Disease

NCT07664930 | Recruiting

• 1 other identifier: POMPE-PHRENIC
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pompe Disease

Keywords

Pompe disease; Phrenic nerve; Diaphragm; Respiratory muscle weakness; Neuromuscular respiratory failure; Motor unit

Outcome Measures

Primary Outcomes (3)

• Motor latency (ms)

  Phrenic nerve conduction parameter measured by bilateral nerve conduction studies

  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

  Baseline (at first available assessment, retrospective or prospective)

• Presence or absence of diaphragmatic responses

  Phrenic nerve conduction parameter assessed bilaterally

  Baseline (at first available assessment, retrospective or prospective)

Secondary Outcomes (4)

• Neurogenic pattern

  Baseline (at time of clinical assessment when EMG is performed)

• Myopathic pattern

  Baseline (at time of clinical assessment when EMG is performed)

• Mixed pattern

  Baseline (at time of clinical assessment when EMG is performed)

• Normal pattern

  Baseline (at time of clinical assessment when EMG is performed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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.

You may not qualify if:

• \- 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.
• 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.

Sponsors & Collaborators

• IRCCS National Neurological Institute "C. Mondino" Foundation: lead
• Fondazione Salvatore Maugeri: collaborator

Study Sites (1)

Translational Neurophysiology

Pavia, 27100, Italy

RECRUITING

Related Publications (6)

• 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.

  PMID: 19474295 BACKGROUND

• Falk 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.

  PMID: 25217571 BACKGROUND

• ElMallah 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.

  PMID: 25569118 BACKGROUND

• Turner 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.

  PMID: 27614205 BACKGROUND

• Oliveira 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.

  PMID: 38653115 BACKGROUND

• Spiesshoefer 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.

  PMID: 31327549 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Giuseppe Cosentino, MD

  Translational Neurophysiology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Cosentino, MD

CONTACT

0382380249; giuseppe.cosentino@mondino.it

Cinzia Fattore, MD

CONTACT

0382380385; cinzia.fattore@unipv.it

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: June 24, 2026
• Study Start: March 30, 2026
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2029
• Last Updated: June 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)