Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive Magnetic Resonance Exploratory Pilot Study.

NCT05943678 | Active Not Recruiting

• 1 other identifier: 1868/2022
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Previous studies have indicated that 13C-MRS in the ultra-high 7T magnetic resonance (MR) field is a potential non-invasive measurement method for assessing changes in muscle glycogen levels in PoD patients. However, in a single study, increases in glycogen intermediates were observed using the even more sensitive 31P-MRS technique in a mouse model of PoD and in glycogen storage disease III in humans. In fact, glycolytic intermediates such as phosphomonoesters (PME), measured by phosphorus-31P-MRS in PoD mouse models, were superior to 13C-MRS in monitoring disease progression and quantifying glycogen, indicating a significant clinical potential of 31P-MRS in humans. It has been shown that 31P-MRS can reliably quantify age- and weight-related differences as well as changes in thyroid function in human muscle metabolism. This study conducted by our institute demonstrates that the technique possesses the necessary sensitivity to measure these subtle muscular metabolic changes. However, there are currently no human 31P-MRS muscle data available for PoD. Therefore, we propose a proof-of-principle study to address this knowledge gap and contribute to establishing a new sensitive muscular biomarker that quantifies the primary disease mechanism, namely glycogen formation, for future longitudinal studies on PoD.

Conditions

Pompe Disease; McArdle Disease

Outcome Measures

Primary Outcomes (1)

• muscle glycogen concentration

  12 months

Secondary Outcomes (1)

• muscle phospho-mono-ester concentration (PME)

  12 months

Study Arms (3)

Healthy controls

negative controls

Device: Siemens Magnetom 7T Plus

Pompe Disease patients

Device: Siemens Magnetom 7T Plus

McArdle Disease patients

positiv controls

Device: Siemens Magnetom 7T Plus

Interventions

Siemens Magnetom 7T Plus DEVICE

Magnetic Resonance Spectroscopy

Healthy controls; McArdle Disease patients; Pompe Disease patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients diagnosed with Pompe or McArdle Disease based on enzyme activity and/or genetic testing Healthy individuals will serve as controls

You may qualify if:

• Patients with PoD and McArdle disease:
• age between 18-70
• Confirmed diagnosis: enzyme activity and/or genetic testing
• body weight \> 40kg at screening
• minute walking distance \> 75m at screening (only PoD patients)
• Sitting FCV ≥ 30% predicted (only PoD patients)
• "Informed Consent" issued orally and in writing
• Healthy volunteers (controls):
• age between 18-70

You may not qualify if:

• Patients with PoD and McArdle disease:
• pregnancy (will be assessed prior to MRS measurements using a rapid pregnancy test)
• Involvement of the respiratory musculature
• claustrophobia
• active participation in another clinical trial
• metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation \[heart pacemaker, coronary stents and heart valves (in case these devices are not compatible with a 7T MRI), brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body.
• Healthy volunteers (controls):
• any known endocrine, metabolic or neurological disorder
• special diets especially ketogenic or atkins diet
• creatine supplementation
• pregnancy (will be assessed prior to MRS measurements using a rapid pregnancy test)
• claustrophobia
• active participation in another clinical trial
• metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation \[heart pacemaker, coronary stents and heart valves (in case these devices are not compatible with a 7T MRI), brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body.

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

Location

Related Publications (4)

• Wary C, Laforet P, Eymard B, Fardeau M, Leroy-Willig A, Bassez G, Leroy JP, Caillaud C, Poenaru L, Carlier PG. Evaluation of muscle glycogen content by 13C NMR spectroscopy in adult-onset acid maltase deficiency. Neuromuscul Disord. 2003 Sep;13(7-8):545-53. doi: 10.1016/s0960-8966(03)00069-5.

  PMID: 12921791 BACKGROUND

• Taylor KM, Meyers E, Phipps M, Kishnani PS, Cheng SH, Scheule RK, Moreland RJ. Dysregulation of multiple facets of glycogen metabolism in a murine model of Pompe disease. PLoS One. 2013;8(2):e56181. doi: 10.1371/journal.pone.0056181. Epub 2013 Feb 14.

  PMID: 23457523 BACKGROUND

• Baligand C, Todd AG, Lee-McMullen B, Vohra RS, Byrne BJ, Falk DJ, Walter GA. 13C/31P MRS Metabolic Biomarkers of Disease Progression and Response to AAV Delivery of hGAA in a Mouse Model of Pompe Disease. Mol Ther Methods Clin Dev. 2017 Sep 8;7:42-49. doi: 10.1016/j.omtm.2017.09.002. eCollection 2017 Dec 15.

  PMID: 29018835 BACKGROUND

• Beiglbock H, Wolf P, Pfleger L, Caliskan B, Fellinger P, Zettinig G, Anderwald CH, Kenner L, Trattnig S, Kautzky-Willer A, Krssak M, Krebs M. Effects of Thyroid Function on Phosphodiester Concentrations in Skeletal Muscle and Liver: An In Vivo NMRS Study. J Clin Endocrinol Metab. 2020 Dec 1;105(12):dgaa663. doi: 10.1210/clinem/dgaa663.

  PMID: 32944774 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum

MeSH Terms

Conditions

Glycogen Storage Disease Type II; Glycogen Storage Disease Type V

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 Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc.Prof. PD Dr.

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: August 15, 2023
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): October 15, 2028
• Last Updated: August 26, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)