Calf Muscle Strength in Mitochondrial Diseases

Study Overview
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Brief Summary
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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
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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.

Official Title
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Calf Muscle Strength in Patients Affected by Mitochondrial Diseases as Compared to Healthy Individuals

Conditions
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Mitochondrial Disease

Intervention / Treatment
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* Other: MRI and muscle dynamometer


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: MRI and muscle dynamometer|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle CCSA, investigated by Dixon MRI techniques. | The MRI protocol include a whole body scan. The calf is chosen for qualitative analysis. Cross sectional area is calculated, the amount of adipose tissue is calculated, and the amount of adipose tissue is subtracted from the CSA, giving the CCSA. | One MRI scan per subject (exam lasts approximately 60 min.) | 
| Muscle strength, measured as peak torque, investigated by an isokinetic dynamometer (Biodex 4). | The dynamometer makes it possible to isolate particular muscle groups. It is possible to control the range of motion and thereby test in an area free of pain. | The tests takes less than an hour and are only done once. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the muscle strength by a clinical test using the Medical Research Council Scale for muscle strength (MRC-scale). |  | The exam lasts 15 min. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Strength, MRI, CCSA, Contractile Cross Sectional Area, Calf muscle