A Randomised, Double-blind, Placebo-controlled, Mono-centre, Explorative Phase II Trial to Study the Effects of Rosuvastatin on Basal Production and Release of Nitric Oxide From the Renal Vasculature in Patients With Hypercholesterolemia.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Change in renal plasma flow from baseline in response to L-NMMA infusion after 6 weeks treatment with rosuvastatin.
研究概览
简要总结
The endothelium plays an important role in the regulation of vascular tone and regulation of blood flow. Nitric oxide (NO) is the most important known endothelium-derived vasodilating factor. Prospective studies have shown that hypercholesterolemia impairs endothelial function in different vascular beds. Lowering total cholesterol and particularly LDL-cholesterol with statins leads to an improvement in endothelium-dependent vasodilation in the forearm vasculature. There is strong evidence to suggest that the benefit is not merely related to the decrease in cholesterol-levels. A recent study in the forearm vasculature demonstrated that short-term lipid-lowering therapy improves endothelial function and NO availability already after 3 days of lipid lowering therapy. Whether endothelial function in the renal vasculature of hypercholesterolemic patients is similarly influenced has not yet been addressed adequately. In the present study we investigate whether lipid lowering therapy with rosuvastatin alters renal endothelial function, as assessed by systemic infusion of the NO synthase inhibitor L-NMMA, after 3 and 42 days of therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female and male patients aged between 18 and 75 years
- •fasting LDL C concentrations >=160 and < 250mg/dl
- •fasting TG concentrations =< 350mg/dl
排除标准
- •History of statin induced myopathy, or serious hypersensitivity reaction to other HMG-CoA reductase inhibitors (statins).
- •History of hypersensitivity reaction to inulin.
- •Lipid-lowering drugs (including lipid lowering dietary supplements of food additives) within the last 4 weeks.
- •Diabetes mellitus, defined as glycosylated hemoglobin (HbA1C) above the upper limit of normal (ULN).
- •Uncontrolled arterial hypertension (>160/100mm Hg).
- •Subjects considered to be unstable (event within 12 weeks) by the investigator after the following events: a myocardial infarction, unstable angina, myocardial revascularisation (PTCA, CABG surgery or another revascularisation procedure) or a transient ischaemic attack (TIA) or stroke.
- •Significant arrythmias or conduction disturbances.
- •Congestive heart failure (NYHA classes III or IV).
- •Pregnant women, women who are breast feeding, and women of childbearing potential who are not using chemical or mechanical contraception or have positive serum pregnancy test (a serum beta-human chorionic gonadotropin analysis).
- •History of homozygous familial hypercholesterolaemia or known type III hyperlipoproteinemia (familial dysbetalipoproteinemia).
- •Use of concomitant medications.
- •Current active liver disease(SGPT > 2xULN) or severe hepatic impairment.
- •Unexplained serum CK > 3 times ULN (e.g. not due to recent trauma, intramuscular injections, heavy exercise etc.).
- •Serum creatinine > 2,0 mg/dl and creatinine clearance <80ml/min.
- •History of nephrolithiasis with calcium oxalate aggregation.
- •Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH) > 1,5 times the UL or subjects whose thyroid replacement therapy was initiated within the last 3 month.
- •Severe disorders of the gastrointestinal tract or other diseases which interfere with the pharmacodynamics and pharmacokinetics of the study drug.
- •History of malignancy(unless a documented disease-free period exceeding 10 years is present) with the exception of basal cell or squamous cell carcinoma of the skin. Women with a history of cervical dysplasia would be permitted to enter the study provided they have 3 consecutive clear Papanicolaou (Pap) smears.
- •History of organ allografts.
- •Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subjects´s safety or successful participation in the trial.
- •Participation in a clinical study within 4 weeks preceding treatment start.
- •Past or present alcohol or drug abuse.
- •Suspected or confirmed poor compliance.
- •Previous enrolment in this study.
结局指标
主要结局
Change in renal plasma flow from baseline in response to L-NMMA infusion after 6 weeks treatment with rosuvastatin.
次要结局
- Change in renal plasma flow from baseline in response to L-NMMA infusion after 3 days treatment with rosuvastatin.
研究者
Roland E. Schmieder
Prof. Dr. med.
University of Erlangen-Nürnberg Medical School