Pompe Disease Clinical Trial
— SPOT_PDOfficial title:
Multispectral Optoacoustic Tomography for Translational Molecular Imaging in Pompe Disease
In patients with Pompe disease (PD) a progressive abnormal lysosomal glycogen storage in muscle tissue leads to impaired muscle function and to degeneration of muscle fibers. Children and adults with PD present with limb-girdle muscular weakness, diaphragm weakness and impaired breathing ability. Further, patients with classic infantile PD suffer from hypertrophic cardiomyopathy. To date, the muscle pathology and the extent of the disease can be assessed using invasive techniques (e.g., muscle biopsies) or imaging (e.g., MRI). These techniques are time consuming, and especially in young patients, require anesthesia, which increases the acute risk of respiratory failure. Multispectral optoacoustic tomography (MSOT) allows the detection of specific endogenous chromophores like collagen, myoglobin or hemoglobin by using a non-invasive approach comparable to conventional ultrasound. Instead of sound waves, MSOT illuminates tissue with near-infrared light of transient energy, which is absorbed and results in thermo-elastic expansion of certain molecules. This expansion generates ultrasound waves that are detected by the same device. Multispectral illumination and unmixing then allows the precise localisation and quantification of muscle-specific subcellular structures. MSOT has already been demonstrated the potential to visualize the muscular structure and the clinical extent of muscular disease in patients with Duchenne muscle dystrophy and differentiates those patients from healthy volunteers. The aim of the study is to establish glycogen as a novel PD-specific imaging target using MSOT-imaging. It intends to identify a PD-specific muscle pathology-signature by quantification of already established targets (collagen, myoglobin, hemoglobin, glycogen if applicable). This signature will aid in differentiating PD from other muscular pathologies and healthy volunteers and will ultimately serve as a potential non-invasive monitoring biomarker.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | December 1, 2022 |
Est. primary completion date | September 1, 2022 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: Pompe disease: - Confirmed diagnosis of Pompe disease - From 18 years of Age - Independent from current therapy Muscular dystrophy: - Genetically confirmed diagnosis - From 18 years of Age - Independent from current therapy Health volunteer: - From 18 years of Age, matched (age, gender) to PD collective Exclusion Criteria: Pompe disease: - Pregnancy - Tattoo on skin to be examined Muscular dystrophy: - Pregnancy - Tattoo on skin to be examined Health volunteer: - Anamnestic of other signs of myopathy or liver disease - Pregnancy - Tattoo on skin to be examined |
Country | Name | City | State |
---|---|---|---|
Germany | University Hospital Erlangen | Erlangen | Bavaria |
Lead Sponsor | Collaborator |
---|---|
University of Erlangen-Nürnberg Medical School |
Germany,
Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, Kissel JT; AANEM Consensus Committee on Late-onset Pompe Disease. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012 Mar;45(3):319-33. doi: 10.1002/mus.22329. Epub 2011 Dec 15. Review. — View Citation
HERS HG. alpha-Glucosidase deficiency in generalized glycogenstorage disease (Pompe's disease). Biochem J. 1963 Jan;86:11-6. — View Citation
Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, Crowley JF, Downs S, Howell RR, Kravitz RM, Mackey J, Marsden D, Martins AM, Millington DS, Nicolino M, O'Grady G, Patterson MC, Rapoport DM, Slonim A, Spencer CT, Tifft CJ, Watson MS. Pompe disease diagnosis and management guideline. Genet Med. 2006 May;8(5):267-88. Erratum in: Genet Med. 2006 Jun;8(6):382. ACMG Work Group on Management of Pompe Disease [removed]; Case, Laura [corrected to Case, Laura E]. — View Citation
Knieling F, Neufert C, Hartmann A, Claussen J, Urich A, Egger C, Vetter M, Fischer S, Pfeifer L, Hagel A, Kielisch C, Görtz RS, Wildner D, Engel M, Röther J, Uter W, Siebler J, Atreya R, Rascher W, Strobel D, Neurath MF, Waldner MJ. Multispectral Optoacoustic Tomography for Assessment of Crohn's Disease Activity. N Engl J Med. 2017 Mar 30;376(13):1292-1294. doi: 10.1056/NEJMc1612455. — View Citation
Regensburger AP, Fonteyne LM, Jüngert J, Wagner AL, Gerhalter T, Nagel AM, Heiss R, Flenkenthaler F, Qurashi M, Neurath MF, Klymiuk N, Kemter E, Fröhlich T, Uder M, Woelfle J, Rascher W, Trollmann R, Wolf E, Waldner MJ, Knieling F. Detection of collagens by multispectral optoacoustic tomography as an imaging biomarker for Duchenne muscular dystrophy. Nat Med. 2019 Dec;25(12):1905-1915. doi: 10.1038/s41591-019-0669-y. Epub 2019 Dec 2. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Optoacoustic Absorption Spectrum of Muscle and liver in PD | Difference in optoacoustic spectrum in patients compared to healthy volunteers | 60 minutes for MSOT, 1 Visit | |
Secondary | Quantitative glycogen signal (in arbitrary units) | Difference of quantitative glycogen signal in Pompe disease patients compared to muscular dystrophy and healthy control | 60 minutes for MSOT, 1 Visit | |
Secondary | Quantitative lipid signal (in arbitrary units) | Difference of quantitative lipid signal in Pompe disease patients compared to muscular dystrophy and healthy control | 60 minutes for MSOT, 1 Visit | |
Secondary | Quantitative collagen signal (in arbitrary units) | Difference of collagen lipid signal in Pompe disease patients compared to muscular dystrophy and healthy control | 60 minutes for MSOT, 1 Visit | |
Secondary | Quantitative hemo/myoglobin signal (in arbitrary units) | Difference of hemo/myoglobin lipid signal in Pompe disease patients compared to muscular dystrophy and healthy control | 60 minutes for MSOT, 1 Visit | |
Secondary | Muscle oxygenation (in %) | Difference of muscle oxygenation in Pompe disease patients compared to muscular dystrophy and healthy control | 60 minutes for MSOT, 1 Visit | |
Secondary | Heckmatt scale | Difference of Heckmatt scale in Pompe disease patients compared to muscular dystrophy and healthy control | 30 minutes for B-mode-ultrasound, 1 Visit | |
Secondary | Echogenitiy | Difference of Echogenitiy in Pompe disease patients compared to muscular dystrophy and healthy control | 30 minutes for B-mode-ultrasound, 1 Visit | |
Secondary | Gray Scale Level | Difference of Gray Scale Level in Pompe disease patients compared to muscular dystrophy and healthy control | 30 minutes for B-mode-ultrasound, 1 Visit | |
Secondary | Ultrasound Guided Attenuation Parameter (UGAP) of liver | Difference of UGAP in Pompe disease patients compared to muscular dystrophy and healthy control | 30 minutes for B-mode-ultrasound, 1 Visit | |
Secondary | R-PaAt scale | Difference of R-PaAt scale in Pompe disease patients compared to muscular dystrophy and healthy control | 10 minutes, 1 Visit | |
Secondary | Revised Upper Limb Module (RULM) | Correlation of glycogen detected by MSOT with clinical scores | 1 hour for total muscle testing, 1 Visit | |
Secondary | MRC Muscle Strength Grades | Correlation of glycogen detected by MSOT with clinical scores | 1 hour for total muscle testing, 1 Visit | |
Secondary | 6-minute-walk-test | Correlation of glycogen detected by MSOT with clinical scores | 1 hour for total muscle testing, 1 Visit | |
Secondary | Stand-up and go test | Correlation of glycogen detected by MSOT with clinical scores | 1 hour for total muscle testing, 1 Visit | |
Secondary | Quick motor function test | Correlation of glycogen detected by MSOT with clinical scores | 1 hour for total muscle testing, 1 Visit | |
Secondary | Respiratory function test (FEV1, FVC) | Correlation of glycogen detected by MSOT with respiratory function test | 20 minutes, 1 Visit | |
Secondary | Functional. magnetic resonance imaging of lung (Ventilation defect, perfusion defect, combined defects) | Correlation of glycogen detected by MSOT with functional magnetic resonance imaging parameters | 1 hour for total MR Imaging, 1 Visit | |
Secondary | Magnetic resonance imaging of biceps muscle | Correlation of glycogen detected by MSOT with magnetic resonance imaging parameters | 1 hour for total MR Imaging, 1 Visit |
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