Sodium-Endothelial Function-CKD Study

This study has been completed.
Sponsor:
Collaborators:
British Heart Foundation
St. George's Hospital Charitable Foundation
Information provided by:
St George's, University of London
ClinicalTrials.gov Identifier:
NCT00141622
First received: August 31, 2005
Last updated: May 14, 2007
Last verified: August 2005
  Purpose

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.


Condition Intervention
Kidney Failure, Chronic
Drug: Slow sodium

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Does Sodium Affect Endothelial Function in Individuals With Chronic Kidney Disease?

Resource links provided by NLM:


Further study details as provided by St George's, University of London:

Primary Outcome Measures:
  • 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

Estimated Enrollment: 50
Study Start Date: April 2005
Estimated Study Completion Date: October 2006
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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00141622

Locations
United Kingdom
Blood Pressure Unit, Department of Cardiac & Vascular Sciences, SGUL
London, United Kingdom, SW17 0RE
Sponsors and Collaborators
St George's, University of London
British Heart Foundation
St. George's Hospital Charitable Foundation
Investigators
Principal Investigator: Timothy WR Doulton, BSc MRCP SGUL
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00141622     History of Changes
Other Study ID Numbers: LREC 04/Q0803/181
Study First Received: August 31, 2005
Last Updated: May 14, 2007
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by St George's, University of London:
Endothelial dysfunction
ADMA
DDAH
Sodium

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic

ClinicalTrials.gov processed this record on September 16, 2014