The Effect of Statin Medications on Muscle Performance (The STOMP Study)

Study Overview
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Brief Summary
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Statins are a group of medications that are used to lower cholesterol levels. Although serious side effects are rare, some people taking statins experience muscle pain or weakness. This study will evaluate the number of people who experience mild muscle complaints and will determine the effect of statins on skeletal muscle strength, endurance, and aerobic exercise performance.

Detailed Description
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Statins are the most effective medications for reducing high cholesterol levels. They are extremely well tolerated by the majority of people but can produce a variety of muscle-related side effects in some people. Of these side effects, the most serious is rhabdomyolysis, which involves muscle fiber damage that can begin as muscle pain and progress to a loss of muscle cells, kidney failure, and death. While rhabdomyolysis is extremely rare, some people experience the more common muscle-related side effects of statins, such as muscle pain (known as myalgia), cramps, and weakness. These more common side effects warrant attention because they may limit the use of statins, affect mobility, and increase the risk of injury in older individuals. Also, the term muscle weakness, often used by patients and their doctors, is not well defined and can refer to a wide range of complaints from simple fatigue to an actual inability to perform activities of daily living. It is important to describe and quantify in more detail the muscle-related side effects associated with statins. The purpose of this study is to determine the incidence of statin-induced mild muscle complaints and to determine the effect of statins on skeletal muscle strength, endurance, and aerobic exercise performance. This study will enroll healthy people who have never received statin medications. First, participants will attend three study visits over a period of 2 weeks. These study visits will include blood collection, questionnaires on physical activity and pain, vital sign measurements, and body measurements, including height, weight, and head circumference. Participants will also complete two cardiopulmonary exercise stress tests on a treadmill and will undergo arm and leg strength testing. Some participants may undergo a muscle biopsy. Participants will then be randomly assigned to receive either 80 mg of atorvastatin or placebo on a daily basis for 6 months. Blood will be collected again at Month 3. At Month 6, participants will attend two study visits for repeat baseline measurements. All participants will be contacted by phone every other week during the 6-month treatment period to monitor adverse events and medication compliance.

Official Title
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The Effect of Statins on Skeletal Muscle Function

Conditions
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Hydroxymethylglutaryl-CoA Reductase Inhibitors, Muscular Diseases

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Statin-naive (i.e., has never taken statins before) Exclusion Criteria: Previous use of statins Current treatment with cholesterol- or triglyceride-lowering drugs Impaired liver or kidney function Untreated hypothyroidism or hyperthyroidism Treatment with other medications known to increase risk of myopathy in atorvastatin-treated patients (e.g., cyclosporine, azithromycin, erythromycin, azole antifungals, fusidic acid) Existing infection requiring treatment with antibiotic therapy Consumption of greater that 1 quart of grapefruit juice per day Documented history of neuroleptic malignant syndrome Inherited muscle disorders or myopathy Known sickle cell trait Cancer within the 5 years prior to study entry Diabetes Currently being treated for high blood pressure Coronary artery disease Peripheral vascular disease Physical disability or previous injury that prevents safe exercise testing Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive atorvastatin for 6 months. | Drug: Atorvastatin<br>* 80-mg atorvastatin capsules taken daily for 6 months<br>* Other names: Lipitor;|
| Placebo Comparator: 2<br>Participants will receive matching placebo for 6 months. | Drug: Placebo<br>* Placebo capsules taken daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myopathy frequency |  | Measured every other week | 
| Arm isokinetic force at 60 degrees per second |  | Measured at Month 6 | 
| Leg isokinetic force at 60 degrees per second |  | Measured at Month 6 | 
| Handgrip isometric force |  | Measured at Month 6 | 
| Leg dynamic endurance |  | Measured at Month 6 | 
| Maximal aerobic power |  | Measured at Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structural differences in the muscle samples obtained from symptomatic and asymptomatic participants |  | Measured after 2 weeks of symptom persistence | 
| Skeletal muscle gene expression in muscle samples obtained from symptomatic and asymptomatic participants |  | Measured after 2 weeks of symptom persistence | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Statins, Myalgia, Muscle Cramp