DNA Diagnostic System for Statin Safety and Efficacy

Hypercholesterolemia Clinical Trial

— SIM  

Official title:

DNA Diagnostic System for Statin Safety and Efficacy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00767130
• Other study ID #: 1 R44 HL091697-01
• Status: Recruiting
• Phase: N/A
• First received: October 2, 2008
• Last updated: October 3, 2008
• Start date: January 2007
• Est. completion date: December 2009

Study information

• Verified date: October 2008
• Source: Genomas, Inc
• Contact: Richard L. Seip, PhD
• Phone: 860-545-5005
• Email: rseip[@]harthosp.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Hypercholesterolemia
• Myopathy

Locations

Country	Name	City	State
United States	Hartford Hospital	Hartford	Connecticut
United States	Rogosin Institute, New York Presbyterian Hospital	New York	New York
United States	University of California-San Francisco	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
Genomas, Inc	Cornell University, Hartford Hospital, University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (2)

Ruaño G, Thompson PD, Windemuth A, Seip RL, Dande A, Sorokin A, Kocherla M, Smith A, Holford TR, Wu AH. Physiogenomic association of statin-related myalgia to serotonin receptors. Muscle Nerve. 2007 Sep;36(3):329-35. — View Citation

Ruaño G, Thompson PD, Windemuth A, Smith A, Kocherla M, Holford TR, Seip R, Wu AH. Physiogenomic analysis links serum creatine kinase activities during statin therapy to vascular smooth muscle homeostasis. Pharmacogenomics. 2005 Dec;6(8):865-72. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	myopathy		in response to statin therapy	Yes
Primary	serum creatine kinase activity		in response to statin therapy	Yes
Secondary	LDL cholesterol		in response to statin therapy	No

External Links

•   Hartford Hospital & the Henry Low Heart Center