Clinical trial NCT01214746: The Effects of Atorvastatin on the Nitric Oxide-system in Healthy Young Man
Official title: The Effects of Atorvastatin on the Nitric Oxide-system in Healthy Young Man
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Diseases
Nephropathy
Keywords: Statin
L-NMMA
Healthy subjects
Nephrology
Lead sponsor: Regional Hospital Holstebro
Sponsor class: OTHER
First posted: 2010-10-05
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Fractional excretion of sodium
timeFrame: 5 days treatment
Secondary outcomes:
measure: Systolic blood pressure (SBP)
timeFrame: 5 days
measure: Pulse wave velocity
timeFrame: 5 days
measure: plasma renin concentration
timeFrame: 5 days
measure: Augmentation index (AI)
timeFrame: 5 days
measure: Diastolic blood pressure
timeFrame: 5 days
measure: Plasma aldosterone concentration
timeFrame: 5 days
measure: Plasma and urinary albumin concentration
timeFrame: 5 days
measure: Urinary excretion of aquaporin-2
timeFrame: 5 days
measure: plasma atrial natriuretic peptide concentration
timeFrame: 5 days
measure: Plasma brain natriuretic peptide concentration
timeFrame: 5 days
measure: 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)
timeFrame: 5 days
Other outcomes:
Locations:
city: Holstebro
country: Denmark
facility: Medicinsk Forskning, Regionshospitalet Holstebro
Study officials:
affiliation: Medicinsk Forskning
name: Frank H Christensen, MD
role: PRINCIPAL_INVESTIGATOR
References: