Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia
Information source: National Taiwan University Hospital
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hyperlipidemia
Intervention: rosuvastatin,fenofibrate (Drug); CYP2C9, UGT1A1, UGT1A3, OATP2, BCRP (Genetic)
Phase: N/A
Status: Available
Sponsored by: National Taiwan University Hospital Overall contact:
chau-chung Wu, Phd, Phone: +886-2-23123456, Ext: 65428, Email: chauchungwu@ntu.edu.tw
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.
Clinical Details
Official title: Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia
Study design: N/A
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.
Eligibility
Minimum age: 20 Years.
Maximum age: 79 Years.
Gender(s): Both.
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.
Locations and Contacts
chau-chung Wu, Phd, Phone: +886-2-23123456, Ext: 65428, Email: chauchungwu@ntu.edu.tw Additional Information
Last updated: July 7, 2009
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