HypercholesterolemiaSIMNCT00767130
DNA Diagnostic System for Statin Safety and Efficacy
An observational study of Hypercholesterolemia and Myopathy, run by Genomas, Inc at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia, Myopathy
- How many people
- 750 participants
- Where
- 3 sitesUnited States
- Study dates
- Jan 2007to Dec 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients treated for hypercholesterolemia at Hartford Hospital, University of California-San Francisco, or the Rogosin Clinic at New York Presbyterian Hospital
Who may be able to join
- 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
Who cannot join
- never having taken any statin medication
Trial locations and contacts
3 sites in 1 country.
United States3 sites, 3 recruiting
- Recruiting
Hartford Hospital
Hartford, Connecticut, 06102
Richard L. Seip, PhD, 860-545-5005, rseip@harthosp.org
Paul D. Thompson, M.D.
- Recruiting
Rogosin Institute, New York Presbyterian Hospital
New York, New York, 10021
Chioma Okoro, 212-702-9600 ext. 105, cokoro@mail.rockefeller.edu
Bruce Gordon, M.D.
- Recruiting
University of California-San Francisco
San Francisco, California, 94110
Alan H.B. Wu, PhD, (415) 206-3540, wualan@labmed2.ucsf.edu
Alan H.B. Wu, PhD
About this study
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.
Read the 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.
- Conditions
- Hypercholesterolemia, Myopathy
- Keywords
- single nucleotide polymorphisms, SNP, LDL cholesterol, statin myopathy, atorvastatin, simvastatin, rosuvastatin
- Medical subject headings
- Hypercholesterolemia, Muscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | receiving atorvastatin | |
| 2 | receiving simvastatin | |
| 3 | receiving rosuvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
myopathy
Measured: in response to statin therapy
serum creatine kinase activity
Measured: in response to statin therapy
Secondary outcomes (1)
LDL cholesterol
Measured: in response to statin therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2008 (estimated)
- Study startJan 2007
- Primary completionDec 2009 (estimated)
- Study completionDec 2009 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 750 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genomas, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hartford Hospital, University of California, San Francisco, Cornell University
- Investigators
- Gualberto Ruano, MD, PhD, Principal investigator, Genomas, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00767130
- Sponsor's protocol ID
- 1 R44 HL091697-01
- Acronym
- SIM
- Status last verified
- Oct 2008
- First submitted
- 2 Oct 2008
- Last updated
- 6 Oct 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 17600820Ruano 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.
PubMed 16296949Ruano 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.
PubMed 27514463Ruano 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.
PubMed 21868014
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DNA Diagnostic System for Statin Safety and Efficacy
- ClinicalTrials.gov ID
- NCT00767130
- Acronym / sponsor ID
- SIM / 1 R44 HL091697-01
- Conditions
- Hypercholesterolemia, Myopathy
- Keywords
- single nucleotide polymorphisms, SNP, LDL cholesterol, statin myopathy, atorvastatin, simvastatin, rosuvastatin
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 750 participants (estimated)
- Lead sponsor
- Genomas, IncIndustry (pharma, biotech, devices)
- Collaborators
- Hartford Hospital, University of California, San Francisco, Cornell University
- Study start
- Jan 2007
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Dec 2009 (estimated)
- First posted
- 6 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –receiving atorvastatin |
| 2 | – | –receiving simvastatin |
| 3 | – | –receiving rosuvastatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients treated for hypercholesterolemia at Hartford Hospital, University of California-San Francisco, or the Rogosin Clinic at New York Presbyterian Hospital
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (1 listed)
- never having taken any statin medication
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
myopathy
Time frame: in response to statin therapy
serum creatine kinase activity
Time frame: in response to statin therapy
1 secondary outcome
LDL cholesterol
Time frame: in response to statin therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2008.
- Background: PubMed 17600820Ruano 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.
- Background: PubMed 16296949Ruano 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.
- Derived from this study: PubMed 27514463Ruano 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.
- Derived from this study: PubMed 21868014Ruano 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.
- Hartford Hospital \& the Henry Low Heart CenterLink provided by the sponsor.
- Rogosin Institute, affiliated with NY Presbyterian Hospital and Weill Cornell School of MedicineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gualberto Ruano, MD, PhD principal investigator
Genomas, Inc
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypercholesterolemia and Myopathy, run by Genomas, Inc at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Oct 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Richard L. Seip, PhD (860-545-5005, rseip@harthosp.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
myopathy (time frame: in response to statin therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00767130, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2008.