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

Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pompe Disease; McArdle Disease
• Intervention / Treatment: Device: Siemens Magnetom 7T Plus

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

Study Locations

• Austria
  • Vienna
    • Vienna, Vienna, Austria, 1090
      • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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

Description

Inclusion criteria

Patients with PoD and McArdle disease:

• age between 18-70
• Confirmed diagnosis: enzyme activity and/or genetic testing
• body weight > 40kg at screening
• 6-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

Exclusion criteria

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls; negative controls	Device: Siemens Magnetom 7T Plus; Magnetic Resonance Spectroscopy
Pompe Disease patients	Device: Siemens Magnetom 7T Plus; Magnetic Resonance Spectroscopy
McArdle Disease patients; positiv controls	Device: Siemens Magnetom 7T Plus; Magnetic Resonance Spectroscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
muscle glycogen concentration	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
muscle phospho-mono-ester concentration (PME)	12 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2023
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): October 15, 2028

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 5, 2023
• First Posted (Actual): July 13, 2023

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Glycogen Storage Disease Type II; Glycogen Storage Disease Type V
• Other Study ID Numbers: 1868/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No