Rosuvastatin and Renal Endothelial Function

NCT00160745 | Completed Phase 2

• 1 other identifier: Rosuvastatin-study
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypercholesterolemia

Keywords

endothelium, NO, renal, statins

Outcome Measures

Primary Outcomes (1)

• Change in renal plasma flow from baseline in response to L-NMMA infusion after 6 weeks treatment with rosuvastatin.

Secondary Outcomes (1)

• Change in renal plasma flow from baseline in response to L-NMMA infusion after 3 days treatment with rosuvastatin.

Interventions

Rosuvastatin DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead
• AstraZeneca: collaborator

Study Sites (1)

CRC, Medizinische Klinik 4 - Nephrology and Hypertension, University of Erlangen-Nürnberg

Erlangen, Krankenhausstrase 12, 91054, Germany

Location

Related Publications (4)

• Ott C, Schlaich MP, Schmidt BM, Titze SI, Schaufele T, Schmieder RE. Rosuvastatin improves basal nitric oxide activity of the renal vasculature in patients with hypercholesterolemia. Atherosclerosis. 2008 Feb;196(2):704-11. doi: 10.1016/j.atherosclerosis.2006.12.020. Epub 2007 Feb 12.

  PMID: 17298834 RESULT

• Ott C, Ritt M, Titze SI, Schaufele T, Schmieder RE. Rosuvastatin does not affect intrarenal hemodynamics in patients with hypercholesterolemia. J Nephrol. 2009 Sep-Oct;22(5):675-81.

  PMID: 19810001 RESULT

• Ott C, Schneider MP, Schlaich MP, Schmieder RE. Rosuvastatin improves pulse wave reflection by restoring endothelial function. Microvasc Res. 2012 Jul;84(1):60-4. doi: 10.1016/j.mvr.2012.03.007. Epub 2012 Mar 29.

  PMID: 22484031 RESULT

• Ott C, Raff U, Schneider MP, Titze SI, Schmieder RE. 25-hydroxyvitamin D insufficiency is associated with impaired renal endothelial function and both are improved with rosuvastatin treatment. Clin Res Cardiol. 2013 Apr;102(4):299-304. doi: 10.1007/s00392-012-0534-1. Epub 2012 Dec 21.

  PMID: 23262496 RESULT

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Roland E Schmieder, MD

  CRC, Medizinsiche Klinik 4 - Nephrology and Hypertension, University of Erlangen-Nürnberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 12, 2005
• Study Completion: September 1, 2006
• Last Updated: February 26, 2018

Record last verified: 2018-02

Locations

DE (1)