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

NCT ID: NCT00431665

Last Updated: 2007-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-07-31
• Study Completion Date: 2000-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

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

Intervention Type: DRUG

triglycerides (Intralipid 20%)

Intervention Type: DRUG

heparin

Intervention Type: DRUG

somatostatin

Intervention Type: DRUG

insulin

Intervention Type: DRUG

glucose

Intervention Type: DRUG

inulin

Intervention Type: DRUG

paraamino hippurate (PAH)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Principal Investigators

Michael Roden, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine III, Medical University of Vienna

Locations

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

OPHT-070699

Identifier Type: -

Identifier Source: org_study_id