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

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Nephropathy
• Intervention / Treatment: Drug: Atorvastatin; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Holstebro, Denmark, 7500
    • Medicinsk Forskning, Regionshospitalet Holstebro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; 1 tablet Unikalk 1 time pr day for 5 days; Other Names: Unikalk
ACTIVE_COMPARATOR: Atorvastatin	Drug: Atorvastatin; Zarator, 80 mg pr day for 5 days; Other Names: Zarator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional excretion of sodium	Sodium excretion measured before, during and after L-NMMA infusion	5 days treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Systolic blood pressure (SBP)	5 days
Pulse wave velocity	5 days
plasma renin concentration	5 days
Augmentation index (AI)	5 days
Diastolic blood pressure	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

Collaborators and Investigators

• Sponsor: Regional Hospital Holstebro
• Investigators: Principal Investigator: Frank H Christensen, MD, Medicinsk Forskning

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): June 1, 2011
• Study Completion (ACTUAL): June 1, 2011

Study Registration Dates

• First Submitted: May 18, 2010
• First Submitted That Met QC Criteria: October 4, 2010
• First Posted (ESTIMATE): October 5, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 16, 2011
• Last Update Submitted That Met QC Criteria: August 15, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Healthy subjects; Statin; Nephrology; L-NMMA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: EBP-FHC-2010-1