Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy Using Multispectral Optoacoustic Tomography

NCT ID: NCT03490214

Last Updated: 2019-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-01
• Study Completion Date: 2018-09-01

Brief Summary

This pilot study aims to assess subcellular muscle structure in patients with Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) in comparison to healthy volunteers using multispectral optoacoustic tomography (MSOT). During MSOT, a transducer is placed on the skin similar to a conventional sonography and instead of sound, energy is supplied to the tissue by means of light flashes. This leads to a constant change of minimal expansions and contractions (thermoelastic expansion) of individual tissue constituents or molecules. The resulting sound waves can then be detected by the same examination unit.

Detailed Description

Duchenne X-linked progressive Duchenne muscular dystrophy (DMD) is one of the most common progressive childhood muscle diseases with an incidence of 1 in 3500 male newborns and is associated primarily with decreased life expectancy. From the age of 4-5 years manifest motor problems in everyday life, typical signs of proximal muscle weakness, with lab-chemical increase of the muscle enzyme (creatinine kinase, CK). Within a few years, relevant muscle and tendon shortening leading to joint malpositions and instability, as well as scoliosis and loss of walking around the age of 10 are formed. Supportive therapies can not curatively affect complications and progression of the disease. Pathogenetically, there is a deficiency of dystrophin, a structural protein of the sarcolemma, which is caused by mutations (usually deletions) of the dystrophin gene (Xp21.3-p21.2). The result of dystrophin deficiency is a necrosis of muscle cells that are replaced by connective tissue and adipose tissue. Clinical scores (6-minute walk test, 6MWT) and MRI studies to characterize the degenerative changes of skeletal muscle in the early stages are available for the quantitative assessment of the disease progression as well as therapy effects, the significance of which is controversially discussed. However, the highly sensitive assessment of gene therapy effects (e.g., PTC 124) will become increasingly important in the future. Sensitive, non-invasive methods for the detection of early muscle degeneration and muscle function in the course are of great clinical and scientific importance. The purpose of this first pilot study is to investigate whether the differences in skeletal muscle composition of healthy volunteers and ambulatory patients with early stage DMD can be quantified and characterized using multispectral optoacoustic tomography (MSOT). This could in the future generate a completely new, non-invasive method to develop non-invasive biomarkers of disease progression or therapy response.

Conditions

Duchenne Muscular Dystrophy; Muscular Dystrophies; Muscular Dystrophy, Duchenne

Keywords

Optoacoustics; MSOT; Multispectral Optoacoustic Tomography

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Muscular Dystrophia

Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: Musculus brachioradialis

Group Type: EXPERIMENTAL

Multispectral Optoacoustic Tomography

Intervention Type: DEVICE

Non-invasive transcutaneous imaging of subcellular muscle components

Healthy Volunteer

Multispectral Optoacoustic Tomography (MSOT) of muscles (left and right, total 8 sites) leg proximal: Musculus quadriceps, distal: Musculus triceps surae arm proximal: Musculus biceps, distal: Musculus brachioradialis

Group Type: ACTIVE_COMPARATOR

Multispectral Optoacoustic Tomography

Intervention Type: DEVICE

Non-invasive transcutaneous imaging of subcellular muscle components

Interventions

Multispectral Optoacoustic Tomography

Non-invasive transcutaneous imaging of subcellular muscle components

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Histologic or genetically proven DMD
• Age 3-10 years

• Male
• Age 3-10 years

Exclusion Criteria

-

Healthy controls

• Suspected muscular disease/myopathia
• missing informed consent

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ferdinand Knieling, Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen

Regina Trollmann, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen

Locations

Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen

Erlangen, Bavaria, Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 31792454 (View on PubMed)

Other Identifiers

67_18 B

Identifier Type: -

Identifier Source: org_study_id