Clinical trial NCT00767130: DNA Diagnostic System for Statin Safety and Efficacy
Official title: DNA Diagnostic System for Statin Safety and Efficacy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypercholesterolemia
Myopathy
Keywords: single nucleotide polymorphisms, SNP, LDL cholesterol, statin myopathy, atorvastatin, simvastatin, rosuvastatin
Lead sponsor: Genomas, Inc
Sponsor class: INDUSTRY
Collaborators: name: Hartford Hospital
name: University of California, San Francisco
name: Cornell University
First posted: 2008-10-06
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients treated for hypercholesterolemia at Hartford Hospital, University of California-San Francisco, or the Rogosin Clinic at New York Presbyterian Hospital

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: myopathy
timeFrame: in response to statin therapy
measure: serum creatine kinase activity
timeFrame: in response to statin therapy
Secondary outcomes:
measure: LDL cholesterol
timeFrame: in response to statin therapy
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California-San Francisco
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New York
country: United States
facility: Rogosin Institute, New York Presbyterian Hospital
state: New York
Study officials:
affiliation: Genomas, Inc
name: Gualberto Ruano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ruano 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. doi: 10.1002/mus.20871.
citation: Ruano 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. doi: 10.2217/14622416.6.8.865.
citation: Ruano G, Seip R, Windemuth A, Wu AH, Thompson PD. Laboratory Medicine in the Clinical Decision Support for Treatment of Hypercholesterolemia: Pharmacogenetics of Statins. Clin Lab Med. 2016 Sep;36(3):473-91. doi: 10.1016/j.cll.2016.05.010. Epub 2016 Jun 24.
citation: Ruano G, Windemuth A, Wu AH, Kane JP, Malloy MJ, Pullinger CR, Kocherla M, Bogaard K, Gordon BR, Holford TR, Gupta A, Seip RL, Thompson PD. Mechanisms of statin-induced myalgia assessed by physiogenomic associations. Atherosclerosis. 2011 Oct;218(2):451-6. doi: 10.1016/j.atherosclerosis.2011.07.007. Epub 2011 Jul 20.