MSOT in Pompe Disease

NCT05083806 | Completed

• 1 other identifier: 21-238_1-B
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pompe Disease; Pompe Disease (Late-onset); Pompe's Disease Juvenile Onset; Pompe Disease Infantile-Onset

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Quantitative glycogen signal (in arbitrary units)

  60 minutes for MSOT, 1 Visit

• Quantitative lipid signal (in arbitrary units)

  60 minutes for MSOT, 1 Visit

• Quantitative collagen signal (in arbitrary units)

  60 minutes for MSOT, 1 Visit

• Quantitative hemo/myoglobin signal (in arbitrary units)

  60 minutes for MSOT, 1 Visit

• Muscle oxygenation (in %)

  60 minutes for MSOT, 1 Visit

Study Arms (2)

Pompe disease

EXPERIMENTAL

Actual condition

Device: Multispectral Optoacoustic Tomography

Healthy volunteer

ACTIVE COMPARATOR

Healthy control

Device: Multispectral Optoacoustic Tomography

Interventions

Multispectral Optoacoustic Tomography DEVICE

Non-invasive optoacoustic imaging of muscular structure

Also known as: MSOT, MSOT Echo, MSOT Echo CE

Healthy volunteer; Pompe disease

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

University Hospital Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Related Publications (6)

• HERS HG. alpha-Glucosidase deficiency in generalized glycogenstorage disease (Pompe's disease). Biochem J. 1963 Jan;86(1):11-6. doi: 10.1042/bj0860011. No abstract available.

  PMID: 13954110 BACKGROUND

• 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.

  PMID: 22173792 BACKGROUND

• 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. doi: 10.1097/01.gim.0000218152.87434.f3. No abstract available.

  PMID: 16702877 BACKGROUND

• Knieling F, Neufert C, Hartmann A, Claussen J, Urich A, Egger C, Vetter M, Fischer S, Pfeifer L, Hagel A, Kielisch C, Gortz RS, Wildner D, Engel M, Rother 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. No abstract available.

  PMID: 28355498 BACKGROUND

• Regensburger AP, Fonteyne LM, Jungert J, Wagner AL, Gerhalter T, Nagel AM, Heiss R, Flenkenthaler F, Qurashi M, Neurath MF, Klymiuk N, Kemter E, Frohlich 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.

  PMID: 31792454 BACKGROUND

• Tan L, Zschuntzsch J, Meyer S, Stobbe A, Bruex H, Regensburger AP, Classen M, Alves F, Jungert J, Rother U, Li Y, Danko V, Lang W, Turk M, Schmidt S, Vorgerd M, Schlaffke L, Woelfle J, Hahn A, Mensch A, Winterholler M, Trollmann R, Heiss R, Wagner AL, Raming R, Knieling F. Non-invasive optoacoustic imaging of glycogen-storage and muscle degeneration in late-onset Pompe disease. Nat Commun. 2024 Sep 8;15(1):7843. doi: 10.1038/s41467-024-52143-6.

  PMID: 39245687 DERIVED

Related Links

• Publication of the clinical study

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

• Regina Trollmann, MD

  University Hospital Erlangen

  STUDY DIRECTOR

• Ferdinand Knieling, MD

  University Hospital Erlangen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study director

Study Record Dates

• First Submitted: October 5, 2021
• First Posted: October 19, 2021
• Study Start: May 17, 2022
• Primary Completion: March 30, 2023
• Study Completion: August 14, 2023
• Last Updated: March 12, 2025

Record last verified: 2025-03

Locations

DE (1)