Nitric Oxide (NO) Activity and Diabetic Nephropathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT00136188
First received: August 25, 2005
Last updated: June 18, 2012
Last verified: June 2012
  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 2
Phase 3

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Role of NO Activity for the Development of Diabetic Nephropathy

Resource links provided by NLM:


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

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

Enrollment: 100
Study Start Date: August 2009
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Folic Acid
    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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00136188

Locations
Germany
CRC, Medizinische Klnik 4 - Nephrology and Hypertension, Uni Erlangen-Nürnberg
Erlangen, Germany, 91054
Sponsors and Collaborators
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
  More Information

Additional Information:
No publications provided by University of Erlangen-Nürnberg Medical School

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT00136188     History of Changes
Other Study ID Numbers: SFB 423 TP B5
Study First Received: August 25, 2005
Last Updated: June 18, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Erlangen-Nürnberg Medical School:
Prediabetes
Metabolic Syndrome
Healthy Controls
Endothelial function

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Folic Acid
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Hematinics
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 08, 2014