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Rosuvastatin and Renal Endothelial Function

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Roland E. Schmieder, University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT00160745
First received: September 6, 2005
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Hypercholesterolemia
Drug: Rosuvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

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: 46
Estimated Study Completion Date: September 2006
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female and male patients aged between 18 and 75 years
  • fasting LDL C concentrations >=160 and < 250mg/dl
  • fasting TG concentrations =< 350mg/dl

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00160745

Locations
Germany
CRC, Medizinische Klinik 4 - Nephrology and Hypertension, University of Erlangen-Nürnberg
Erlangen, Krankenhausstrase 12, Germany, 91054
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
AstraZeneca
Investigators
Principal Investigator: Roland E Schmieder, MD CRC, Medizinsiche Klinik 4 - Nephrology and Hypertension, University of Erlangen-Nürnberg
  More Information

No publications provided

Responsible Party: Roland E. Schmieder, Prof. Dr. med., University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT00160745     History of Changes
Other Study ID Numbers: Rosuvastatin-study
Study First Received: September 6, 2005
Last Updated: January 18, 2013
Health Authority: 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:
Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Rosuvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014