DNA Diagnostic System for Statin Safety and Efficacy

Study Overview
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Brief Summary
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Lipitor®, Zocor®, and Crestor® are statin drugs commonly taken to lower cholesterol and prevent heart disease. Statins lower cholesterol by different amounts in different patients and sometimes statins cause muscle pain, cramps, or weakness. This study will examine genetic differences in the blood of patients taking statins to predict both how well the statins lower cholesterol, and whether muscle discomfort occurs. Finding such genetic connections is the key to developing genetic tests that might eventually help determine which statin is best for a patient. About 1000 people will be in the study.

Detailed Description
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Statin efficacy in primary and secondary prevention of cardiovascular disease has led to increasingly aggressive usage and dosage of statins. Their main clinically relevant safety risk is statin-induced myopathy (SIM) evidenced as a constellation of neuromuscular side effects (NMSE) that include myalgias (muscle aches, cramps, weakness) and myositis (monitored by elevation of serum creatine kinase [CK] activity). NMSEs are disabling to 3-20% of patients on statins, require alteration of therapy, and reduce compliance. NMSEs vary in extent between drugs and from patient to patient. We will develop a novel product termed SIM PhyzioType™ system to provide clinicians with individualized information for each patient on the safest statin drug among atorvastatin, simvastatin, and rosuvastatin, the 3 most prescribed statins. The PhyzioType consists of a multi-SNP (single nucleotide polymorphism) ensemble that, interpreted with a biomathematical algorithm, predicts drug response. We have developed a prototype PhyzioType system incorporating predictive models for myalgia, serum CK activity, and LDLc reduction for atorvastatin and simvastatin patients. We will recruit to obtain 250 patients treated with each drug and use existing clinical records to characterize their NMSE and LDLc responses. We will use physiogenomic analysis to identify those SNPs that differentiate the risk of NMSEs among the 3 statins and combine them into the SIM PhyzioType system. This work will also contribute to the pharmacology of SIM and unravel new pharmaceutical targets. We will create and validate the SIM PhyzioType system with clinically useful prediction of NMSEs and potency for each of the 3 statins. In Phase III a prospective trial is planned for FDA approval of the SIM PhyzioType product.

Official Title
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DNA Diagnostic System for Statin Safety and Efficacy

Conditions
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Hypercholesterolemia, Myopathy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: receiving, or documented to have received in the past, any of the statins including atorvastatin, simvastatin, rosuvastatin treatment for hypercholesterolemia chart-documented clinical record of having had, never having had, or possibly having had, statin-associated myopathy Exclusion Criteria: never having taken any statin medication

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>receiving atorvastatin | |
| 2<br>receiving simvastatin | |
| 3<br>receiving rosuvastatin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myopathy |  | in response to statin therapy | 
| serum creatine kinase activity |  | in response to statin therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LDL cholesterol |  | in response to statin therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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single nucleotide polymorphisms, SNP, LDL cholesterol, statin myopathy, atorvastatin, simvastatin, rosuvastatin