Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia

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ClinicalTrials.gov Identifier: NCT00934258

Expanded Access Status : Available

First Posted : July 8, 2009

Last Update Posted : December 21, 2012

Sponsor:

Information provided by (Responsible Party):

National Taiwan University Hospital

Study Description

Brief Summary:

Previous studies indicate that the variant status of detoxification proteins is different among Taiwanese and other ethnic groups. For example, in Taiwanese, the major SNPs of CYP2C9 are CYP2C9*2 (430C>T) and CYP2C9*3 (1075A>C) and their frequencies are different from that in Caucasians [11]. The second example is that the frequency of the A(TA)7TAA allele in the promoter area of the UGT1A1 gene is substantially lower, while for the rate of variation within the coding region is much higher in Taiwanese than that in Caucasians (14.3% vs. 35.7- 41.5% and 29.3% vs. 0.1%, respectively) [12]. The third example is that the frequency of 388A>G of the OATP2 gene in Taiwanese (0.68) [13] is in between that in European Americans (0.30) and African Americans (0.74) [14]. Therefore, the investigators hypothesize that, in Taiwanese the SNPs of detoxification proteins modulate the lipid-lowing effects of RVA and fenofibrate may be different from those for Caucasians.

Condition or disease	Intervention/treatment
Hyperlipidemia	Drug: rosuvastatin,fenofibrate Genetic: CYP2C9, UGT1A1, UGT1A3, OATP2, BCRP

Detailed Description:

Since April 2008, we have started to run a multicenter, prospective, randomized, open-label, blinded end-point classification trial to test the hypothesis in Taiwan that the addition of fibrate on statin would provide a further reduction in the major coronary events in the patients with diabetes or atherosclerotic vascular diseases with metabolic syndrome. With the advantage of this large-scaled prospective trial, it is also a good opportunity to identify simultaneously the genetic determinants of wide range of interindividual variability in phenotypic and clinical response to two major lipid-lowering drug classes, rosuvastatin and fenofibrate. The aim of this proposal is to find which SNPs influence the therapeutic effectiveness of lipid lowering therapy in Taiwanese hyperlipidemic patients. A key feature is the use of multiple drug-treated population samples to get the findings derived from both candidate gene and genome-wide searches for SNP associations with markers of drug efficacy as well as side effects. Thus the promise of pharmacogenomics and metabolomics-- "individualized medicine" will come true in treating hyperlipidemia in Taiwanese.

Study Design


Study Type :	Expanded Access
Official Title:	Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Genes and Gene Therapy

Drug Information available for: Fenofibrate Rosuvastatin calcium Rosuvastatin

U.S. FDA: Expanded Access (Compassionate Use)

U.S. FDA Resources

Interventions

Intervention Details:

Drug: rosuvastatin,fenofibrate
Rosuvastatin 10 mg once daily Rosuvastatin 5 mg + SFC fenofibrate 80 mg
Genetic: CYP2C9, UGT1A1, UGT1A3, OATP2, BCRP
All potential patients will be screened for the eligibility in a screening visit. Those who fill the inclusion criteria at screening will be invited for the registry study into different groups. The follow-up will take place at months 6, 12, 18, and every year thereafter for another 3 years, through clinical visiting, phone follow-up, or records from the NHIB Taiwan. At each clinical visit, vital signs, clinical endpoints, adverse events, concurrent medication information and laboratory specimens will be obtained as complete as possible. With phone or records from NHIB, only clinical endpoints will be recorded. If the primary care physician intends to treat the patient's lipid profile to the target, he/she can add, delete or adjust the LLT by his/her clinical judgement

Eligibility Criteria

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Ages Eligible for Study:	20 Years to 79 Years (Adult, Older Adult)
Sexes Eligible for Study:	All

Criteria

Inclusion Criteria:

Men or women aged 20-79 years with definite DM or atherosclerotic vascular diseases with metabolic syndrome, defined as the presence of three or more of the following risk factors:
- abdominal obesity (waist circumference > 90 cm in men or > 80 cm in women),
- triglycerides > 150 mg/dL, HDL-cholesterol < 40 mg/dL in men or < 50 mg/dL in women,
- blood pressure > 130/85 mm Hg, or
- fasting glucose > 100 mg/dL).
Those who are qualified for lipid lowering therapy according to the Taiwanese national guidelines (LDL-C 130-190 mg/dL or TG 200-500 mg/dL with HDL-C < 40 mg/dL or TC/HDL-C > 5).

Exclusion Criteria:

Any known contraindications to statin or fibrate therapy,
Previous intolerance to statin or fibrate in low or high doses,
Liver enzyme levels more than 3 times the upper limit of normal,
Pregnancy or breastfeeding,
Nephrotic syndrome,
Uncontrolled diabetes mellitus (HbA1c > 9),
Uncontrolled hypothyroidism,
Plasma LDL-C level higher than 190 mg/dL or triglyceride level higher than 500 mg/dL,
Coronary heart disease event or revascularisation within a month,
Congestive heart failure (New York Heart Association classification IIIb or IV),
Hemodynamically important valvular heart disease,
Gastrointestinal conditions affecting absorption of drugs,
Treatment with other drugs that seriously affect the pharmacokinetics of statins or fibrate,
Unexplained creatine phosphokinase concentrations six or more times the upper limit of normal,
Life-threatening malignancy,
Treatment with immuno suppressive or other lipid lowering drugs.
Patients previously treated with monotherapy with statins or fibrates will be qualified if they have not already had titration to a dose higher than the equivalent of 5 mg/d of rosuvastatin or 160 mg/d of SFC fenofibrate.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00934258

Contacts


Contact: chau-chung Wu, Phd	+886-2-23123456 ext 65428	chauchungwu@ntu.edu.tw

Sponsors and Collaborators

National Taiwan University Hospital

More Information


Responsible Party:	National Taiwan University Hospital
ClinicalTrials.gov Identifier:	NCT00934258 History of Changes
Other Study ID Numbers:	200812111R 200812111R
First Posted:	July 8, 2009 Key Record Dates
Last Update Posted:	December 21, 2012
Last Verified:	November 2012

Keywords provided by National Taiwan University Hospital:


genes rosuvastatin fenofibrate Cardiovascular (CV) diseases	dyslipidemia metabolic syndrome identify genetic determinants of the wide range of interindividual variability in phenotypic and clinical response to the lipid-lowering drug classes identify genetic susceptibility to drug-related side effects.

Additional relevant MeSH terms:


Hyperlipidemias Hyperlipoproteinemias Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Rosuvastatin Calcium Fenofibrate	Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors

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