Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myopathy
Conditions
Keywords
Statin, Myopathy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atrogin-1
Brief summary
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
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.
Interventions
DRUGsimvastatin
simvastatin 80 mg PO daily for one to eight months.
Sponsors
Scripps Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 90 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Atrogin-1 expression. | One to eight months. |
| Intramuscular Ras level. | One to eight months. |
Secondary
| Measure | 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. |
Countries
United States
Outcome results
None listed