POMPE: Novel Metabolic Muscular Biomarkers in Pompe Disease - a Non-invasive Magnetic Resonance Exploratory Pilot Study.
Study Details
Study Description
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 (Wary et al., 2003). 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 (Taylor et al., 2013) and in glycogen storage disease III in humans (Wary et al., 2010). 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 (Baligand et al., 2017), 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 (Beiglböck et al., 2020). 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | 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
|
Outcome Measures
Primary Outcome Measures
- muscle glycogen concentration [12 months]
Secondary Outcome Measures
- muscle phospho-mono-ester concentration (PME) [12 months]
Eligibility Criteria
Criteria
Inclusion criteria
Patients with PoD and McArdle disease:
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age between 18-70
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Confirmed diagnosis: enzyme activity and/or genetic testing
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body weight > 40kg at screening
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6-minute walking distance > 75m at screening (only PoD patients)
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Sitting FCV ≥ 30% predicted (only PoD patients)
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"Informed Consent" issued orally and in writing
Healthy volunteers (controls):
• age between 18-70
Exclusion criteria
Patients with PoD and McArdle disease:
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pregnancy (will be assessed prior to MRS measurements using a rapid pregnancy test)
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Involvement of the respiratory musculature
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claustrophobia
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active participation in another clinical trial
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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):
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any known endocrine, metabolic or neurological disorder
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical University of Vienna | Vienna | Austria | 1090 |
Sponsors and Collaborators
- Medical University of Vienna
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 1868/2022