Clinical trial NCT01208701: The Effects of Atorvastatin on the Nitrogen Oxide-system in Patients With Type 2 Diabetes and Nephropathy
Official title: The Effect of Atorvastatin on the NO-system in Patients With Type 2 Diabetes and Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Nephropathy
Cardiovascular Diseases
Diabetes Mellitus
Keywords: Atorvastatin
L-NMMA
NO
Nephrology
Diabetes Mellitus
Lead sponsor: Regional Hospital Holstebro
Sponsor class: OTHER
First posted: 2010-09-24
Enrollment: 25
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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 patients with type 2 diabetes with nephropathy.

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.

Eligibility criteria: Inclusion Criteria:

* Men and women
* minimum 40 years
* Chronic Kidney disease
* Estimated GFR (eGFR) between 30 and 90 ml/min
* Diabetes Mellitus type II

Exclusion Criteria:

* Nephrotic Syndrome
* Anamnestic or clinical signs of significant heart, lung, lever, kidney and brain disease
* Neoplastic disease
* Alcohol abuse,
* Drug abuse
* Pregnancy or nursing
* Blood donation within a month before examination
* Hgb \< 6,0

Primary outcomes:
measure: Fractional excretion of sodium
timeFrame: 5 days treatment
Secondary outcomes:
measure: Systolic blood pressure
timeFrame: 5 days
measure: Plasma renin concentration
timeFrame: 5 days
measure: Arterial stiffness
timeFrame: 5 days
measure: Plasma angiotensin II 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
measure: Augmentations index
timeFrame: 5 days
Other outcomes:
Locations:
city: Holstebro
country: Denmark
facility: Medicinsk Forskning, Regionshospitalet Holstebro
Study officials:
affiliation: Department of Medical Research
name: Frank H Christensen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mose FH, Larsen T, Jensen JM, Hansen AB, Bech JN, Pedersen EB. Effect of atorvastatin on renal NO availability and tubular function in patients with stage II-III chronic kidney disease and type 2 diabetes. Scand J Clin Lab Invest. 2014 Jan;74(1):8-19. doi: 10.3109/00365513.2013.855942. Epub 2013 Nov 21.