The Effects of Atorvastatin on the Nitrogen Oxide-system in Patients With Type 2 Diabetes and Nephropathy

Phase 2

Completed

• Conditions: Nephropathy; Cardiovascular Diseases; Diabetes Mellitus
• Interventions: Drug: Atorvastatin; Drug: Unikalk

• Registration Number: NCT01208701
• Lead Sponsor: Erling Bjerregaard Pedersen

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.

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-09-19
• Study First Submitted QC: 2010-09-23
• Study First Posted: 2010-09-24
• Primary Completion: 2012-01
• Study Completion: 2012-01
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-19
• Last Update Posted: 2015-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin	-
Placebo	Unikalk	-

Primary Outcome Measures

Name	Time	Method
Fractional excretion of sodium	5 days treatment

Secondary Outcome Measures

Name	Time	Method
Systolic blood pressure	5 days
Plasma renin concentration	5 days
Arterial stiffness	5 days
Plasma angiotensin II 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
Augmentations index	5 days

Trial Locations

Locations (1)

Medicinsk Forskning, Regionshospitalet Holstebro; 🇩🇰 Holstebro, Denmark