Endothelin Receptor Antagonism in Proteinuric Nephropathy

July 23, 2008 updated by: University of Edinburgh

The Systemic & Renal Effects of Endothelin Receptor Antagonism in Proteinuric Nephropathy

The number of people with kidney problems is increasing rapidly, related in part to the increasing prevalence of diabetes. Patients with kidney problems tend to have protein leaking into the urine (proteinuria). Both proteinuria and the kidney disease itself are associated with an increased risk of heart disease. Reducing proteinuria is an important treatment goal in people with kidney problems. Endothelin is a chemical produced both by blood vessels and the kidney. Higher than normal levels of endothelin are thought to contribute to progression of kidney disease and proteinuria. By using drugs that block the effects of endothelin ('endothelin receptor antagonists') we can hopefully reduce both of these. The purpose of the study is to ascertain whether endothelin receptor antagonists improve kidney function and reduce proteinuria more so than other commonly used drugs.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Response to ETA Receptor Antagonism/Nifedipine/Placebo Prior to the study visit subjects will be asked to refrain from alcohol for 24 hours. Tea and coffee will not be permitted for at least 12 hours before each visit. Studies will be conducted in a quiet, temperature-controlled room.

On arrival at the Clinical Research Centre on the study day, a brief medical enquiry and examination will confirm the ongoing suitability of the subject for the study. An intravenous cannula will be inserted into the antecubital fossa of each arm. We have developed a basic protocol described fully in our previous studies that allows us to measure systemic haemodynamics by the well validated technique of bioimpedance and renal function by standard para-aminohippurate (PAH; renal blood flow) and inulin (glomerular filtration rate) clearance studies.

Urinary protein excretion will be measured by collecting urine over 30 minute time periods. To ascertain the contribution of renal haemodynamics to any change in protein excretion renal blood flow and glomerular filtration rate will be measured. In addition, blood and urine will also be assayed for sodium, creatinine and osmolality to allow calculation of fractional excretion of sodium and free water clearance.

Systemic haemodynamic monitoring will be performed at 15 minute intervals during drug/placebo administration and at 30 minute intervals outwith these periods.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 1

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
    • Scotland
      • Edinburgh, Scotland, United Kingdom, EH4 2XU
        • Clinical Research Centre, Western General Hospital

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female
  • Age 18-70
  • Body mass index <35
  • Blood pressure <160/110 mmHg
  • CKD stage 2-5 as per the K/DOQI classification
  • Proteinuria in one of the following categories: 0.3-1.5, >1.5-3.0, and >3.0-6.0 g/24hrs
  • Normal serum albumin

Exclusion Criteria:

  • Subject is below the age of legal consent, or is mentally or legally incapacitated
  • History of multiple and/or severe allergic reactions to drugs (including study drugs), or food
  • The subject has donated blood (450 ml) within the last 4 weeks
  • Past or present drug or alcohol abuse including intravenous drug abuse at any time
  • Participation in another clinical trial within 1 month
  • Considered to be at high risk of HIV or hepatitis B
  • Pregnant

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 1
Placebo control arm of study
Drug: 0.9 % saline
Single 15ml 0.9% saline infused for 15 mins as placebo control
Experimental: 2
BQ-123 arm of study
Drug: BQ-123 (selective endothelin A receptor antagonist)
Single dose of BQ-123 given at a dose of 1000 nmol/min for 15 min intravenously.
Active Comparator: 3
Nifedipine arm of study
Drug: Nifedipine
Single dose of nifedipine 10 mg given orally as active control
Other Names:
  • Adalat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Proteinuria
Time Frame: Acute change in proteinuria over 4 hour period following BQ-123 dosing
Acute change in proteinuria over 4 hour period following BQ-123 dosing
Blood pressure
Time Frame: Acute change in blood pressure over 4 hour period following BQ-123 dosing
Acute change in blood pressure over 4 hour period following BQ-123 dosing

Secondary Outcome Measures

Outcome Measure
Time Frame
Arterial stiffness (as measured by pulse wave velocity)
Time Frame: Acute change in arterial stiffness over 4 hour period following BQ-123 dosing
Acute change in arterial stiffness over 4 hour period following BQ-123 dosing
Endothelial function (as measured by flow-mediated dilatation)
Time Frame: Acute change in endothelial function over 4 hour period following BQ-123 dosing
Acute change in endothelial function over 4 hour period following BQ-123 dosing

Collaborators and Investigators

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

Sponsor

University of Edinburgh

Collaborators

British Heart Foundation

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

May 1, 2006

Primary Completion (Actual)

November 1, 2007

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

July 23, 2008

First Submitted That Met QC Criteria

July 23, 2008

First Posted (Estimate)

July 25, 2008

Study Record Updates

Last Update Posted (Estimate)

July 25, 2008

Last Update Submitted That Met QC Criteria

July 23, 2008

Last Verified

August 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2006/WCRC/02
  • PG/05/91
  • 06/MRE00/12

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.

Clinical Trials on Proteinuria

Clinical Trials on 0.9 % saline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Japan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe