Rosuvastatin and Renal Endothelial Function
This study has been completed.
Information provided by (Responsible Party):
Roland E. Schmieder, University of Erlangen-Nürnberg Medical School
First received: September 6, 2005
Last updated: January 18, 2013
Last verified: January 2013
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.
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Prevention
||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.
Primary Outcome Measures:
- Change in renal plasma flow from baseline in response to L-NMMA infusion after 6 weeks treatment with rosuvastatin.
Secondary Outcome Measures:
- Change in renal plasma flow from baseline in response to L-NMMA infusion after 3 days treatment with rosuvastatin.
| Estimated Enrollment:
| Estimated Study Completion Date:
|Ages Eligible for Study:
||18 Years to 75 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Female and male patients aged between 18 and 75 years
- fasting LDL C concentrations >=160 and < 250mg/dl
- fasting TG concentrations =< 350mg/dl
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00160745
|CRC, Medizinische Klinik 4 - Nephrology and Hypertension, University of Erlangen-Nürnberg
|Erlangen, Krankenhausstrase 12, Germany, 91054 |
University of Erlangen-Nürnberg Medical School
||Roland E Schmieder, MD
||CRC, Medizinsiche Klinik 4 - Nephrology and Hypertension, University of Erlangen-Nürnberg
No publications provided
||Roland E. Schmieder, Prof. Dr. med., University of Erlangen-Nürnberg Medical School
History of Changes
|Other Study ID Numbers:
|Study First Received:
||September 6, 2005
||January 18, 2013
||Germany: Federal Institute for Drugs and Medical Devices
Keywords provided by University of Erlangen-Nürnberg Medical School:
endothelium, NO, renal, statins
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 21, 2013
Lipid Metabolism Disorders
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents