The Effects of Exercise Versus Inactivity on People With Mitochondrial Muscle Disease
Summary
Mitochondrial myopathies include various inherited diseases that are caused by damage to the mitochondria, energy-producing structures that fuel the body's processes. The main symptoms are muscle weakness, reduced muscle mass, and difficulty with exercising. The purpose of this study is to determine the effects of exercise training versus inactivity on mitochondrial function in muscle and muscle performance in people with mitochondrial myopathies.
Description
Mitochondrial myopathies are caused by mutant mitochondrial DNA, genetic defects in parts of the mitochondrial DNA. These defects can include missing or deleted DNA that typically codes for certain proteins involved in energy production. These mutations cause individual mitochondria and the body on a whole to produce energy less efficiently. Because muscle cells require extensive energy to function properly, they are particularly impaired by mitochondrial dysfunction. The onset of most mitochondrial myopathies occurs before the age of 20. Initially a person may experience muscle weakness and fatigue during physical activity. Other symptoms may include limited eye mobility, heart arrhythmias, slurred speech, swallowing difficulties, and impaired movement.
There is no cure yet for mitochondrial myopathies, nor is there any adequate treatment to stall disease progression. Exercise, known to boost the production and function of mitochondria in healthy people, may reduce symptoms in people with mitochondrial myopathies by increasing the number and function of normal mitochondria in an individual muscle cell. The purpose of this study is to determine the effects of exercise training versus inactivity on the expression of normal and mutant mitochondrial DNA and on mitochondrial production within muscle cells in people with mitochondrial myopathies. The study will also assess how cell function, physical endurance, heart function, and quality of life are affected by exercise training and inactivity.
Participants in this 2-year study will first undergo physiological exercise testing, magnetic resonance imaging (MRI) of heart and skeletal muscles, a needle biopsy of muscle, and a questionnaire on quality of life. Participants will then be randomly assigned to partake in regular exercise training or no training for 6 months. After 6 months, all participants will undergo repeat testing of initial evaluations. Participants who had been in the exercising group will then switch to no exercise training for 6 months, and participants who had been in the non-exercising group will switch to regular exercise training for 6 months. The second 6-month period will also be followed by repeat testing of initial evaluations. Participants will then be encouraged to continue exercise training for an additional 1 year, with retesting at the end of the second year. Each of the four evaluations will take about 15 hours over 5 days.
Study Design
Allocation: Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Mitochondrial Myopathy
Intervention
Exercise
Location
University of Texas Southwestern Medical Center
Dallas
Texas
United States
75321
Status
Recruiting
Source
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00457314
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Exercise Tolerance
The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an EXERCISE TEST.
Exercise Test
Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate.
Merrf Syndrome
A mitochondrial encephalomyopathy characterized clinically by a mixed seizure disorder, myoclonus, progressive ataxia, spasticity, and a mild myopathy. Dysarthria, optic atrophy, growth retardation, deafness, and dementia may also occur. This condition tends to present in childhood and to be transmitted via maternal lineage. Muscle biopsies reveal ragged-red fibers and respiratory chain enzymatic defects. (From Adams et al., Principles of Neurology, 6th ed, p986)
Ophthalmoplegia, Chronic Progressive External
A mitochondrial myopathy characterized by slowly progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. Ragged-red fibers and atrophy are found on muscle biopsy. Familial and sporadic forms may occur. Disease onset is usually in the first or second decade of life, and the illness slowly progresses until usually all ocular motility is lost. (From Adams et al., Principles of Neurology, 6th ed, p1422)
Asthma, Exercise-induced
Asthma attacks following a period of exercise. Usually the induced attack is short-lived and regresses spontaneously. The magnitude of postexertional airway obstruction is strongly influenced by the environment in which exercise is performed (i.e. inhalation of cold air during physical exertion markedly augments the severity of the airway obstruction; conversely, warm humid air blunts or abolishes it).
Clinical Trials
Pilot Compassionate Use Study of Thioctic Acid Treatment in Mitochondrial Myopathy
OBJECTIVES: I. Assess the efficacy of thioctic acid in treating a single patient with mitochondrial myopathy.
Intensive Exercise to Improve Mitochondrial Dysfunction in Pediatric Obesity
Obesity and type 2 diabetes are occurring at epidemic rates in the United States and worldwide. The global burden of diabetes is estimated to double over the next 25 years. Obese children...
An association between insulin resistance and mitochondrial dysfunction has been observed in aging, T2D, and in offspring of patients with T2D. It remains to be determined whether pharmac...
Phase III Trial of Coenzyme Q10 in Mitochondrial Disease
Our central hypothesis is that oral CoQ10 is a safe and effective treatment for children with inborn errors of mitochondrial energy metabolism due to defects in specific respiratory chain...
There is now a general consensus that the combination of excessive energy intake and a low capacity to oxidize fat will lead to muscular fat accumulation and insulin resistance. It is know...
PubMed Articles
Metabolic myopathies: functional evaluation by different exercise testing approaches.
Metabolic myopathies are a clinically and etiologically heterogeneous group of disorders due to defects in muscular energy metabolism. They include glycogen storage diseases, fatty acid oxidation defe...
Mitochondrial myopathies: developments in treatment.
PURPOSE OF REVIEW: Treatment options for mitochondrial myopathies remain limited despite rapid advances in the understanding of the molecular basis of these conditions. Existing therapies continue to...
Statin therapy, myopathy and exercise--A case report.
ABSTRACT: In a bid to reduce the morbidity and mortality associated with coronary artery disease, statin therapy has become a cornerstone treatment for patients with dyslipideamia. Statins, or HMG-CoA...
BACKGROUND: Mitochondrial myopathy comprises various clinical subforms of neuromuscular disorders that are characterised by impaired mitochondrial energy metabolism due to dysfun...
Axial myopathy is a rare neuromuscular disease that is characterized by paraspinal muscle atrophy and abnormal posture, most notably camptocormia (also known as bent spine). The genetic cause of famil...
