Clinical trial NCT03490214: Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy Using Multispectral Optoacoustic Tomography
Official title: Non-invasive Imaging of Muscle Structure in Duchenne Muscular Dystrophy as Diagnostic and Progression Marker Using Multispectral Optoacoustic Tomography
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Duchenne Muscular Dystrophy
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Keywords: Optoacoustics
MSOT
Multispectral Optoacoustic Tomography
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2018-04-06
Enrollment: 20
Sex: MALE
Minimum age (years): 3
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: DMD-Patients

Inclusion Criteria:

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

Exclusion Criteria:

-

Healthy controls

Inclusion Criteria:

* Male
* Age 3-10 years

Exclusion Criteria:

* Suspected muscular disease/myopathia
* missing informed consent

Primary outcomes:
measure: Muscular lipid content
timeFrame: Single time point (1 day)
measure: Muscular collagen content
timeFrame: Single time point (1 day)
Secondary outcomes:
measure: Muscular myo-/hemoglobin content
timeFrame: Single time point (1 day)
measure: Correlation of lipid signal with age/disease duration
timeFrame: Single time point (1 day)
measure: Correlation of myo-/hemoglobin signal with age/disease duration
timeFrame: Single time point (1 day)
measure: Correlation of lipid signal with 6MWT
timeFrame: Single time point (1 day)
measure: Correlation of lipid signal with MRC
timeFrame: Single time point (1 day)
measure: Correlation of collagen signal with 6MWT
timeFrame: Single time point (1 day)
measure: Correlation of collagen signal with MRC
timeFrame: Single time point (1 day)
measure: Correlation of myo-/hemoglobin signal with 6MWT
timeFrame: Single time point (1 day)
measure: Correlation of myo-/hemoglobin signal with MRC
timeFrame: Single time point (1 day)
measure: Signal differences left and right muscles
timeFrame: Single time point (1 day)
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
state: Bavaria
Study officials:
affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
name: Ferdinand Knieling, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen
name: Regina Trollmann, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.