Clinical trial NCT02678637: Calf Muscle Strength in Mitochondrial Diseases
Official title: Calf Muscle Strength in Patients Affected by Mitochondrial Diseases as Compared to Healthy Individuals
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Mitochondrial Disease
Keywords: MRI
CCSA
Contractile Cross Sectional Area
Strength
Calf muscle
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2016-02-10
Enrollment: 37
Sex: ALL
Minimum age (years): 18
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 mitochondrial disease.

Brief summary: Mitochondrial disorders are a group of inherited disorders causing malfunctional mitochondria. Mitochondria are found in every cell of the body, and the disorders therefore give symptoms from every tissue, especially those with high energy needs as the brain, heart and muscles. The disorders are highly disabling.

The aim of the study is to investigate the relation between muscle strength and contractile cross sectional area (CCSA) in the leg of patients affected by mitochondrial diseases. The hypothesis is that there can be a disrupted relationship between strength and CCSA.

Detailed description: Mitochondrial disorders are a group of inherited disorders caused by mutations in genes encoding mitochondrial proteins. The proteins are encoded by genes from both the mitochondrial DNA (mtDNA) and the nucleus, making some of the disorders maternally inherited and some autosomal recessive or dominant.

The mitochondria are found in almost all cells in the body and are the main source of energy. The energy is produced through the electron transport chain, which is composed of four multi subunit complexes (I to IV). A mutation in one or more of these complexes is a typical cause of a mitochondrial disease.

Since the mitochondria are found in almost every cell, mitochondrial disease can give rise to symptoms from many organs. The symptoms depend on what kind of mutation the patient has, but usually includes muscular and neurological problems, as these cells have especially high energy needs.

It is believed that the muscle weakness in mitochondrial diseases is caused by the reduced ability to produce energy. However, recent research has suggested that there is a structural change in the muscles as well. The hypothesis is that this structural change in the muscles will affect its function.

The aim of the study is to investigate the relation between muscle strength and contractile cross sectional area (CCSA) in the calf of patients affected by mitochondrial diseases. In healthy individuals there is a close relation between strength and CCSA, as the strength will decrease according to a decrease in CCSA. In mitochondrial disease, the hypothesis is that there can be a disrupted relationship between strength and CCSA.

The investigators will recruit 30 subjects with verified mitochondrial disease, and compare the results to that of healthy individuals (results from an earlier research project). A Dixon MRI will be used to find the CCSA of the calf muscle and a muscle dynamometer will be used to find the strength. These two variables are compared.

Eligibility criteria: Inclusion Criteria:

* Verified mitochondrial 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: One MRI scan per subject (exam lasts approximately 60 min.)
measure: Muscle strength, measured as peak torque, investigated by an isokinetic dynamometer (Biodex 4).
timeFrame: The tests takes less than an hour and are only done once.
Secondary outcomes:
measure: Assessment of the muscle strength by a clinical test using "the Medical Research Council Scale for muscle strength" (MRC-scale).
timeFrame: The exam lasts 15 min.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
state: Copenhagen East
Study officials:
affiliation: Copenhagen Neuromuscular Center
name: Nanna S Nielsen, B.Sc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lightowlers RN, Taylor RW, Turnbull DM. Mutations causing mitochondrial disease: What is new and what challenges remain? Science. 2015 Sep 25;349(6255):1494-9. doi: 10.1126/science.aac7516. Epub 2015 Sep 24.
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.