Sodium-Endothelial Function-CKD Study

May 14, 2007 updated by: St George's, University of London

Does Sodium Affect Endothelial Function in Individuals With Chronic Kidney Disease?

Heart disease and stroke, known as cardiovascular disease, are major causes of death in people with chronic kidney disease. Abnormalities of a metabolic pathway called the "L-arginine-nitric oxide" pathway are thought to be particularly important in these people, and previous research in animals has suggested that sodium (salt) affects part of this metabolic pathway. The purpose of our research is to study the effects of sodium intake on the "L-arginine-nitric oxide" pathway, and on blood vessel function, in patients with kidney disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic kidney disease (CKD) is associated with abnormalities of endothelial function (EF) and nitric oxide (NO) synthesis, and it is proposed that the endogenous NO synthase inhibitor asymmetrical dimethylarginine (ADMA) plays a central role. In man ADMA is largely metabolized by dimethylarginine dimethylaminohydrolase (DDAH), with some renal excretion occurring. Sodium inhibits DDAH expression in experimental animals and, given that CKD is frequently characterized by sodium retention, it would be interesting to study the effects of sodium loading on DDAH activity/expression, ADMA levels and EF in CKD patients.

To answer these questions, we have designed a double-blind cross-over study employing Slow Sodium (150 mmol/day) and placebo for seven days in individuals with mild-to-moderate CKD. Changes in the ratio of urinary ADMA to dimethylamine (DMA, an ADMA metabolite) will be used as an marker of DDAH activity/expression. ADMA will be measured by ELISA, DMA by high performance liquid chromatography, and EF by venous occlusion plethysmography.

We propose to test the following hypothesis; that in subjects with mild-to-moderate CKD under conditions of high sodium intake, as compared to low-normal sodium intake:

(i) The ratio [ADMA]urine:[DMA]urine is increased (ii) [ADMA]plasma is increased (iii) Endothelium-dependent vasodilatation is reduced

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

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

  • United Kingdom
      • London, United Kingdom, SW17 0RE
        • Blood Pressure Unit, Department of Cardiac & Vascular Sciences, SGUL

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 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • CKD Stages 2 and 3 [= calculated creatinine clearance of 30 to 89 ml/min/1.73m2 by Cockcroft-Gault formula]
  • 18 to 75 years old

Exclusion Criteria:

  • >3 g/24 hours of proteinuria
  • Uncontrolled hypertension (systolic BP >160 mmHg, diastolic BP >100 mmHg on/off anti-hypertensive medication)
  • Diabetes mellitus
  • Tobacco smoking
  • Total fasting cholesterol >6 mmol/L
  • Uncontrolled heart failure or active IHD
  • Chronic liver failure
  • Active malignancy

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Under conditions of high (vs. low sodium intake) ...
(i) The ratio [ADMA]urine:[DMA]urine is increased
(ii) [ADMA]plasma is increased
(iii) Endothelium-dependent vasodilatation is reduced

Collaborators and Investigators

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

Sponsor

St George's, University of London

Collaborators

British Heart Foundation
St. George's Hospital Charitable Foundation

Investigators

  • Principal Investigator: Timothy WR Doulton, BSc MRCP, SGUL

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

April 1, 2005

Study Completion

October 1, 2006

Study Registration Dates

First Submitted

August 31, 2005

First Submitted That Met QC Criteria

August 31, 2005

First Posted (Estimate)

September 1, 2005

Study Record Updates

Last Update Posted (Estimate)

May 15, 2007

Last Update Submitted That Met QC Criteria

May 14, 2007

Last Verified

August 1, 2005

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LREC 04/Q0803/181

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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