Clinical trial NCT03018184: Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies
Official title: Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies Compared to Healthy Controls
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Inherited Muscle Diseases
Congenital Myopathy
RYR1-myopathy
Keywords: MRI
CCSA
Contractile Cross Sectional Area
Strength
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2017-01-11
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with verified inherited muscle disease.

Brief summary: Patients with inherited muscle diseases can have several problems in their muscles, which can be both structural and metabolic. All the different diseases can affect the contractility of the muscles. The aim of the study is to investigate the relation between muscle strength and contractile cross sectional area (CCSA) in the thigh and calf in patients affected by inherited muscle diseases.

Detailed description: Patients with inherited muscle diseases can have several miscellaneous problems in their muscles, which can be both structural and metabolic. Depending on the specific disease multiple symptoms may be present. All the different diseases can affect the contractility of the muscles. Examples of inherited muscle diseases are congenital myopathies and RYR1-myopathy, afflicting the muscle fiber structure. They are the first subgroups of inherited muscle diseases to be investigated in this study. Congenital myopathies are hereditary and relatively non-progressive diseases. Hypotonia is the clinical characteristic of congenital myopathies and is often presented already in the neonatal period. Almost all patients have generalized muscle weakness and hypotonia. The various subtypes of congenital myopathy are a broad group of disorders defined by the predominance of particular and specific structural abnormalities shown in muscle biopsies. Based on genetic and morphological features, they can be divided into four main groups; one with central cores, one with central nuclei, one with minicores and one with nemaline bodies. RYR1-myopathy is caused by a mutation in the RYR-gene. The RYR1-protein is important in the making of RYR1-receptors and channels responsible for the transport of calcium atoms within muscle cells, particularly in muscle contractions. Patients typically present with limb weakness, decreased fetal movement and skeletal abnormalities. About 70% of patients with malignant hyperthermia have a mutation in the RYR1-gene. MRI findings often include involvement of different muscles in the thigh and the calf.

Eligibility criteria: Inclusion Criteria:

* Verified inherited muscle disease.
* Age: Over 18 years old

Exclusion Criteria:

* Contraindications for an MRI.
* Claustrophobia.
* Pregnant or nursing women.
* Competing disorders (as arthritis) or other muscle disorders.

Primary outcomes:
measure: Muscle CCSA, investigated by Dixon MRI techniques.
timeFrame: MRI scan per subject lasts approximately 60 minutes.
measure: Muscle strength, measured as peak torque, investigated by an isokinetic dynamometer (Biodex 4).
timeFrame: The tests takes less than an hour per subject.
Secondary outcomes:
measure: Muscle Strength, MRC
timeFrame: The exam lasts less than 15 min per subject.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen Neuromuscular Center, Rigshospitalet
Study officials:
affiliation: Copenhagen Neuromuscular Center, Rigshospitalet
name: John Vissing, MD DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Congenital Myopathies: Background, Pathophysiology, Epidemiology [Internet]. [henvist 18. oktober 2016]. Tilgængelig hos: http://emedicine.medscape.com/article/1175852-overview
citation: Hilton-Jones D, Martin R. Turner. Oxford Textbook of Neuromuscular Disorders. I: Oxford Textbook of Neuromuscular Disorders. Oxford; s. 277-87.
citation: Congenital Myopathies Clinical Presentation: History, Causes [Internet]. [henvist 18. oktober 2016]. Tilgængelig hos: http://emedicine.medscape.com/article/1175852-clinical
citation: Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, Bittner C, Fialka-Moser V. Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. 2008 Aug;40(8):665-71. doi: 10.2340/16501977-0235.
citation: Lokken N, Hedermann G, Thomsen C, Vissing J. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I. Ann Neurol. 2016 Sep;80(3):466-71. doi: 10.1002/ana.24743. Epub 2016 Aug 10.