Nitric Oxide (NO) Activity and Diabetic Nephropathy - Full Text View

Sponsor:	University of Erlangen-Nürnberg
Information provided by:	University of Erlangen-Nürnberg
ClinicalTrials.gov Identifier:	NCT00136188

Purpose

Experimental data suggest that oxidative stress and endothelial dysfunction are key players in the pathogenesis of diabetic nephropathy. In the last few years the investigators were able to establish a method to assess endothelial function of the renal vasculature in humans and started to systematically study a variety of cardiovascular disorders known to be associated with endothelial dysfunction in other vascular beds, including hypertension, hypercholesterolemia and type-2 diabetes. In patients with type-2 diabetes the investigators could demonstrate that despite unaltered basal and stimulated NO-activity, the renal response to the antioxidant vitamin C was more pronounced compared to control subjects. These data suggest that oxidative stress is increased in the renal vasculature of diabetic patients. Furthermore, NO-activity in diabetic patients appears to be upregulated to compensate for the increase in oxidative stress. This hypothesis is supported by the demonstration of increased endothelial nitric oxide synthase (eNOS) expression in kidney biopsies of diabetic patients.

The major focus of the investigators' current research activities is to assess the role of endothelial dysfunction in the very early stages of diabetic nephropathy. To this end, patients with increased fasting glucose or metabolic syndrome will be studied in comparison with an age-matched control group. Endothelial function and the role of oxidative stress will be assessed in the renal vasculature in all groups. In parallel, the investigators will study endothelial function in the forearm by venous occlusion plethysmography and in the retinal vasculature by scanning laser doppler flowmetry to dissect regional differences in the regulation of endothelial function. Further aspects include the role of microalbuminuria, glomerular hyperfiltration, and endogenous inhibitors of NO synthase such as NG,NG-Dimethyl-L-Arginine (ADMA). In a therapeutic approach, the investigators will determine the effects of various antioxidant treatment strategies on endothelial function and their potential role in the prevention of diabetic nephropathy.

Condition	Intervention	Phase
Diabetic Nephropathies	Drug: Folic Acid	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment
Official Title:	Role of NO Activity for the Development of Diabetic Nephropathy

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetic Kidney Problems High Blood Pressure

Drug Information available for: Folic acid

U.S. FDA Resources

Further study details as provided by University of Erlangen-Nürnberg:

Primary Outcome Measures:

Change in renal endothelial function [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	August 2009
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Intervention Details:

oral administration of folic acid 5mg /d for 4 weeks

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Male and female patients aged 18-65 with diabetes, prediabetes or metabolic syndrome
Male and female healthy control subjects aged 18-65

Exclusion Criteria:

Advanced damage of vital organs (grade III and IV retinopathy)
Therapy with a not approved concomitant medication in the last 4 weeks prior to intake of the first trial medication, especially lipid lowering and antidiabetic medications (washout phase)
Blood donation within the last 4 weeks
Patients with arterial fibrillation or atrioventricular (AV)-block (II and more)
Patients with anamnestic myocardial infarct
Patients with depression
Patients with seizure disorders
Patients with unstable angina pectoris including electrocardiogram (ECG)-aberrations or cardiac insufficiency New York Heart Association (NYHA) Stadium III and IV
History of a malignant illness with the exception of those patients who have recovered for more than 10 years or have a basalioma of the skin.
Actual or anamnestic alcohol or drug abuse
History of organ transplant
Anaphylaxis or known therapy resistance to any of the used test matters.
Therapy with a not approved concomitant therapy
Participation in another study within three months prior to study inclusion
Illnesses, which can influence the pharmacodynamics or pharmacokinetics of the test substance
Liver or kidney diseases; SGOT, GPT, γ-GT, AP, bilirubin and creatinine above 200% of standard
Patients who are not sufficiently compliant, or patients who are not capable or willing to appear for controlling visits
Severe or unstable medical or psychiatric illnesses, which will, in the estimation of the examiner, endanger the safety of the proband or the successful participation in the study
Presumed risk of transmission of HIV or hepatitis via blood from the proband

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00136188

Contacts

Contact: Roland E Schmieder, MD	++49 (0)9131 853 ext 6245	Roland.Schmieder@uk-erlangen.de
Contact: Markus P Schlaich, MD

Locations

Germany
CRC, Medizinische Klnik 4 - Nephrology and Hypertension, Uni Erlangen-Nürnberg	Recruiting
Erlangen, Germany, 91054
Contact: Roland E. Schmieder, MD ++49 (0)9131 853 ext 6245 roland.schmieder@uk-erlangen.de
Contact: Markus P Schlaich, MD
Principal Investigator: Roland E Schmieder, MD
Principal Investigator: Markus P Schlaich, MD

Sponsors and Collaborators

University of Erlangen-Nürnberg

Investigators

Principal Investigator:	Roland E Schmieder, MD	CRC, Medizinische Klnik 4 - Nephrology and Hypertension, Uni Erlangen-Nürnberg
Principal Investigator:	Markus P Schlaich, MD	CRC, Medizinische Klnik 4 - Nephrology and Hypertension, Uni Erlangen-Nürnberg

More Information

Additional Information:

website

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Prof. Roland E. Schmieder ( University of Erlangen-Nurnberg )
Study ID Numbers:	SFB 423 TP B5
Study First Received:	August 25, 2005
Last Updated:	October 27, 2009
ClinicalTrials.gov Identifier:	NCT00136188 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Erlangen-Nürnberg:

Prediabetes
Metabolic Syndrome
Healthy Controls
Endothelial function

Additional relevant MeSH terms:

Diabetic Nephropathies
Vitamin B Complex
Hematinics
Growth Substances
Hematologic Agents
Physiological Effects of Drugs
Diabetes Mellitus
Endocrine System Diseases

Pharmacologic Actions
Folic Acid
Urologic Diseases
Therapeutic Uses
Vitamins
Kidney Diseases
Micronutrients
Diabetes Complications

ClinicalTrials.gov processed this record on November 27, 2009