Effect of Elevated Plasma-Free-Fatty-Acids on Renal Hemodynamic Parameters

NCT00431665 | Completed

• 1 other identifier: OPHT-070699
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes is frequently associated with elevation of plasma-free fatty acids (FFA). Studies indicate that elevation of plasma-FFA induces insulin resistance and also causes endothelial dysfunction as well as hemodynamic changes which are supposed to be involved in the pathogenesis of diabetic vascular disorders. Glomerular hyperfiltration, which is associated with glomerular hypertension and hypertrophy, a common finding in the early course of type 1 diabetes as well as type 2 diabetes, plays an important role in the development and progression of diabetic nephropathy. These hemodynamic changes are not well understood, but are most likely induced by dilatation of the (precapillary) glomerular arteriole. In humans the hemodynamic effect of FFAs has so far been investigated locally in brachial and femoral arteries and recently in the eye and skin, where FFAs induced a pronounced increase in blood flow probably due to a local decrease in vascular resistance. The aim of the present study is to characterise the hemodynamic effects of FFAs in the kidney. In addition we want to test the hypothesis that FFA-induced changes are mediated via endothelial derived nitric oxide (NO). The results of this study could provide information to what extent elevated FFA-plasma levels contribute to hyperfiltration in the early course of diabetes mellitus. The measurements will be done at baseline and during 4 hour infusion of a triglyceride or placebo infusion, combined with heparin.

Conditions

Renal Circulation; Renal Plasma Flow; Glomerular Filtration Rate; Fatty Acids, Nonesterified

Keywords

Renal Plasma Flow; Glomerular Filtration Rate; Free fatty acids

Outcome Measures

Primary Outcomes (2)

• Renal plasma flow

• Glomerular filtration rate

Interventions

NG-monomethyl-L-Arginine (L-NMMA) DRUG

triglycerides (Intralipid 20%) DRUG

heparin DRUG

somatostatin DRUG

insulin DRUG

glucose DRUG

inulin DRUG

paraamino hippurate (PAH) DRUG

Eligibility Criteria

• Age: 19 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men aged between 19 and 35 years
• Body mass index between 15th and 85th percentile (Must et al. 1991)
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant

You may not qualify if:

• Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study
• Evidence of hypertension, pathologic hyperglycemia, hyperlipidemia
• Treatment in the previous 3 weeks with any drug
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with distribution, metabolism or excretion of study drugs
• History of hypersensitivity to the trial drug or to drugs with a similar chemical structure

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, 1090, Austria

Location

MeSH Terms

Interventions

omega-N-Methylarginine; Triglycerides; Heparin; Somatostatin; Insulin; Glucose; Inulin

Intervention Hierarchy (Ancestors)

Arginine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Glycerides; Lipids; Glycosaminoglycans; Polysaccharides; Carbohydrates; Pituitary Hormone Release Inhibiting Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pancreatic Hormones; Neuropeptides; Peptides; Nerve Tissue Proteins; Proteins; Proinsulin; Insulins; Hexoses; Monosaccharides; Sugars; Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Fructans

Study Officials

• Michael Roden, MD

  Department of Internal Medicine III, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 5, 2007
• First Posted: February 6, 2007
• Study Start: July 1, 1999
• Study Completion: June 1, 2000
• Last Updated: February 6, 2007

Record last verified: 2007-02

Locations

AU (1)