The Effects of Atorvastatin on the Nitric Oxide-system in Healthy Young Man

Phase 2

Completed

• Conditions: Cardiovascular Diseases; Nephropathy
• Interventions: Drug: Placebo; Drug: Atorvastatin

• Registration Number: NCT01214746
• Lead Sponsor: Regional Hospital Holstebro

Brief Summary

It has been documented that statin reduce mortality and morbidity in patients with cardiovascular disease. This effect can partly be related to a reduction in cholesterol levels in blood. Nitric oxide (NO) production is reduced in several chronic diseases such as nephropathy, diabetes and hypertension. The purpose of this study is to investigate the effect of Atorvastatin treatment on the NO-system measuring renal and cardiovascular variables in healthy man.

Detailed Description

Subjects will be examined on two examination days. 4 days prior to each examination day subjects are treated with either atorvastatin or placebo. During treatment periods subject are given a standardized diet.

On the examination days subject are given L-NMMA(L-NG-monomethyl Arginine citrate), a NO inhibitor, 6 mg bolus infusion followed by continuous 4 mg/kg/hr infusion for 1 hour. Renal function, central hemodynamic and vasoactive hormones are evaluated prior, during and after L-NMMA infusion.

Renal function is measured by renal clearance of 51Cr-EDTA and urinary sodium, potassium and albumin concentration. Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC)will be measured to evaluate channel activity in the nephron.

Central blood pressure, pulse wave analysis, and augmentation index are measured using SphygmoCor® from Atcor.

The vasoactive hormones aldosterone, renin, angiotensin II, atrial natriuretic peptide (ANP), brain natriuretic (BNP) and endothelin is measured in plasma

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-05-18
• Study First Submitted QC: 2010-10-04
• Study First Posted: 2010-10-05
• Primary Completion: 2011-06
• Study Completion: 2011-06
• Status Verified: 2011-08
• Last Update Submitted: 2011-08-15
• Last Update Posted: 2011-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Men and women, age 18-40 years
• Body Mass Index (BMI) 18,5-30 kg/m2

Exclusion Criteria

• Arterial hypertension (>140 mmHg systolic and/or 90 mmHg diastolic)
• Anamnestic or clinical signs of heart, lung, lever, kidney and brain disease
• Neoplastic disease
• Alcohol abuse,
• Drug abuse
• Medical treatment except oral anticontraceptive
• Smoking
• Pregnancy or
• Abnormal blood and urine sample
• Abnormal ECG
• Blood donation within a month before examination

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Atorvastatin	Atorvastatin	-

Primary Outcome Measures

Name	Time	Method
Fractional excretion of sodium	5 days treatment	Sodium excretion measured before, during and after L-NMMA infusion

Secondary Outcome Measures

Name	Time	Method
Diastolic blood pressure	5 days
Systolic blood pressure (SBP)	5 days
Pulse wave velocity	5 days
plasma renin concentration	5 days
Augmentation index (AI)	5 days
Plasma aldosterone concentration	5 days
Plasma and urinary albumin concentration	5 days
Urinary excretion of aquaporin-2	5 days
plasma atrial natriuretic peptide concentration	5 days
Plasma brain natriuretic peptide concentration	5 days
Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC)	5 days

Trial Locations

Locations (1)

Medicinsk Forskning, Regionshospitalet Holstebro; 🇩🇰 Holstebro, Denmark