Nitric Oxide (NO) Activity and Diabetic Nephropathy

June 18, 2012 updated by: University of Erlangen-Nürnberg Medical School

Role of NO Activity for the Development of Diabetic Nephropathy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Erlangen, Germany, 91054
        • CRC, Medizinische Klnik 4 - Nephrology and Hypertension, Uni Erlangen-Nürnberg

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in renal endothelial function
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Erlangen-Nürnberg Medical School

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

August 25, 2005

First Submitted That Met QC Criteria

August 25, 2005

First Posted (Estimate)

August 26, 2005

Study Record Updates

Last Update Posted (Estimate)

June 19, 2012

Last Update Submitted That Met QC Criteria

June 18, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SFB 423 TP B5

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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