Multispectral Optoacoustic Tomography for Advanced Imaging of Centronuclear Myopathy

NCT ID: NCT07021820

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-05-29
• Study Completion Date: 2026-12-31

Brief Summary

Twenty patients with centronuclear myopathy and twenty age- and sex-matched, muscle-healthy controls will undergo diagnostic examination. Study participants will undergo physical examination, clinical and functional testing, and multispectral optoacoustic tomography (MSOT) scanning at predefined muscle sites (paraspinal muscles, trapezius muscle, deltoid muscle, forearm flexors, quadriceps muscle, adductor muscles, ischiocrural muscles, triceps surae muscle, and tibialis anterior).

Detailed Description

Centronuclear myopathy (CNM) belongs to the group of congenital myopathies. These are named after their histopathological feature: the nucleus is localized in the center of the muscle cell instead of its physiological position at the periphery. CNM is so rare that there are only epidemiological data available for the group of congenital myopathies as a whole. The incidence is estimated at 0.06 per 1,000 live births.

CNM is genetically and clinically heterogeneous. Identified gene mutations affect proteins involved in membrane remodeling, transport, and excitation-contraction coupling.

Patients with CNM usually present with muscle weakness and hypotonia in early childhood. The severity of the disease varies depending on the underlying genotype and ranges from reduced exercise tolerance and ptosis to floppy infant syndrome and respiratory failure. One example of a very severe course is the X-linked form caused by a Myotubularin 1 (MTM1) nonsense mutation (XL-MTM). Affected patients become symptomatic in the neonatal period and usually die in childhood or adolescence. In contrast, patients with the Dynamin 2 (DNM2) mutation have a later onset and milder disease progression. In the few reported patients with Bridging Integrator 1 (BIN1) mutations, onset occurs in infancy or adulthood with a moderate disease course. Ryanodine receptor 1 (RYR1)-associated CNMs also vary in terms of age of onset and disease severity.

Diagnosis is based on molecular genetic testing and muscle biopsy. However, these techniques are not widely available, are time-consuming, and invasive. Anesthesia is usually required for young patients.

Multispectral optoacoustic tomography (MSOT) enables the detection of specific endogenous chromophores such as collagen, myoglobin, or hemoglobin using a non-invasive approach comparable to conventional ultrasound. Instead of sound waves, MSOT uses near-infrared light pulses that are absorbed by tissue, causing thermoelastic expansion of certain molecules. This expansion generates ultrasound waves, which are then detected by the same device. The multispectral illumination and signal unmixing enable precise localization and quantification of muscle-specific subcellular structures. MSOT has already demonstrated the potential to visualize muscle structure and disease extent in patients with Duchenne muscular dystrophy, spinal muscular atrophy, and late-onset Pompe disease (LOPD), and to distinguish these patients from healthy volunteers. To date, there are no optoacoustic data available for CNM.

The aim of this study is to gain molecular insights into muscle degeneration in CNM patients for the first time. To develop a comprehensive picture of the optoacoustic characteristics of CNM, patients of different ages and disease severities will be recruited. Due to the rarity and small number of CNM cases, recruitment is challenging. Therefore, the opportunity should be taken to offer study participation to as many patients as possible at the patient meeting in Bad Nauheim from May 29 to June 1, 2025. In addition to non-invasive, radiation-free imaging, clinical-functional tests will be conducted as part of the study. These include muscle strength testing (MRC score) and the timed "get up and go" test. Various accessible muscle groups will be scanned using MSOT, including the paraspinal muscles and trapezius muscle, as well as the following limb muscles on both sides: deltoid, biceps brachii, forearm flexors, quadriceps femoris, adductors, hamstrings (ischiocrural muscles), triceps surae, and tibialis anterior.

Conditions

Centronuclear Myopathy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

CNM

patients with diagnosed centronuclear myopathy

MSOT

Intervention Type: DIAGNOSTIC_TEST

Multispectral optoacoustic tomography (MSOT) enables the detection of specific endogenous chromophores such as collagen, myoglobin or haemoglobin using a non-invasive approach comparable to conventional ultrasound. Instead of sound waves, MSOT illuminates the tissue with near-infrared light of transient energy, which is absorbed and leads to thermoelastic expansion of certain molecules. This expansion generates ultrasound waves that are detected by the same device. The multispectral illumination and unmixing then enable the precise localization and quantification of muscle-specific subcellular structures. MSOT has already shown the potential to visualize the muscle structure and clinical extent of muscle disease in patients with Duchenne muscular dystrophy, spinal muscular atrophy and the late-onset Pompe disease (LOPD) and to distinguish these patients from healthy volunteers. To date, there is no optoacoustic data on CNM.

HV

Healthy control

MSOT

Intervention Type: DIAGNOSTIC_TEST

Multispectral optoacoustic tomography (MSOT) enables the detection of specific endogenous chromophores such as collagen, myoglobin or haemoglobin using a non-invasive approach comparable to conventional ultrasound. Instead of sound waves, MSOT illuminates the tissue with near-infrared light of transient energy, which is absorbed and leads to thermoelastic expansion of certain molecules. This expansion generates ultrasound waves that are detected by the same device. The multispectral illumination and unmixing then enable the precise localization and quantification of muscle-specific subcellular structures. MSOT has already shown the potential to visualize the muscle structure and clinical extent of muscle disease in patients with Duchenne muscular dystrophy, spinal muscular atrophy and the late-onset Pompe disease (LOPD) and to distinguish these patients from healthy volunteers. To date, there is no optoacoustic data on CNM.

Interventions

MSOT

Multispectral optoacoustic tomography (MSOT) enables the detection of specific endogenous chromophores such as collagen, myoglobin or haemoglobin using a non-invasive approach comparable to conventional ultrasound. Instead of sound waves, MSOT illuminates the tissue with near-infrared light of transient energy, which is absorbed and leads to thermoelastic expansion of certain molecules. This expansion generates ultrasound waves that are detected by the same device. The multispectral illumination and unmixing then enable the precise localization and quantification of muscle-specific subcellular structures. MSOT has already shown the potential to visualize the muscle structure and clinical extent of muscle disease in patients with Duchenne muscular dystrophy, spinal muscular atrophy and the late-onset Pompe disease (LOPD) and to distinguish these patients from healthy volunteers. To date, there is no optoacoustic data on CNM.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Exclusion Criteria

• Pregnancy
• Nursing mothers
• Tattoo in the area of the examination field
• Subcutaneous fatty tissue > 3 cm

HV:

• any signs/history of muscle diseases
• Pregnancy
• Nursing mothers
• Tattoo in the area of the examination field
• Subcutaneous fatty tissue > 3 cm

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Ferdinand Knieling

Study Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ferdinand Knieling, PD Dr. med. habil. Dr. rer. b

Role: STUDY_CHAIR

Kinder- & Jugendklinik, Erlangen

Locations

Uniklinikum Erlangen

Erlangen, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Lina Tan

Role: CONTACT

Lina.Tan@uk-erlangen.de

+49 9131 85-41277

Facility Contacts

Ferdinand Knieling, PD Dr. med. habil. Dr. rer. b

Role: primary

ferdinand.knieling@uk-erlangen.de

09131-8541337

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

25-120-Bm

Identifier Type: -

Identifier Source: org_study_id