Muscle Characteristics Associated With Statin Therapy

Study Overview
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Brief Summary
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The purpose of this study is to investigate the mechanism of statin-related myopathy by evaluating muscle samples before and after statin exposure.

Detailed Description
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Statins have been proven to reduce cardiovascular events and mortality in large clinical trials but remain underutilized partly due to the associated myopathy. Severe reactions manifested as rhabdomyolysis are rare but myalgia is commonly noted in clinical practice. The pathophysiology of these events remains obscure. Previous studies suggest that statins block the downstream products (such as cellular signaling molecules) of the mevalonate pathway needed for normal muscle function. Other studies show that statins are associated with gene expressions involved in muscle damage such as atrogin-1. We will quantify these entities pre and post statin therapy to better understand these reactions.

Official Title
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Muscle Characteristics Associated With Statin Therapy

Conditions
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Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myopathy

Intervention / Treatment
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* Drug: simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary surgeon's permission. Patient is > 21 years of age. Patient will go through a two phase surgery with the two procedures one to eight months apart. Patient or representative understands the nature of the study. Normal thyroid stimulating hormone (TSH). LDL-cholesterol > 100 mg/dL or highly sensitive C-reactive protein (hsCRP) > 2.0. One of the following risk factors: male > 45 year old or female > 55 year old, smoker, hypertension, first degree family history of coronary artery disease < 55 year old, HDL <40 mg/dL, chronic kidney disease, diabetes mellitus, previous TIA or stroke, previous coronary artery disease. Exclusion Criteria: Has been on a lipid-lowering medication previously. Severe illness (e.g. trauma or sepsis) more than 24 hours before obtaining the first biopsy. Less than a 10% reduction of LDL after 3 months of therapy (indicative of non-adherence). Contraindications to statins such as liver failure. History of underlying muscle disorder. Taking amiodarone.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 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

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Statin exposure<br>Subjects' endpoints will be measured before and after one to eight months of statin exposure. | Drug: simvastatin<br>* simvastatin 80 mg PO daily for one to eight months.<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrogin-1 expression. |  | One to eight months. | 
| Intramuscular Ras level. |  | One to eight months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intramuscular Coenzyme Q10 level. |  | One to eight months. | 
| Intramuscular mitochondrial to nuclear DNA ratio. |  | One to eight months. | 
| Intramuscular geranylgeranylpyrophosphate. |  | One to eight months. | 
| PPAR-gamma coactivator-1-alpha expression. |  | One to eight months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Statin, Myopathy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atrogin-1