Endothelin Receptor Antagonism in Proteinuric Nephropathy - Full Text View

Sponsors and Collaborators:	University of Edinburgh British Heart Foundation
Information provided by:	University of Edinburgh
ClinicalTrials.gov Identifier:	NCT00722215

Purpose

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.

Condition	Intervention	Phase
Chronic Kidney Disease Proteinuria	Drug: BQ-123 (selective endothelin A receptor antagonist) Drug: 0.9 % saline Drug: Nifedipine	Phase I

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	The Systemic & Renal Effects of Endothelin Receptor Antagonism in Proteinuric Nephropathy

Resource links provided by NLM:

MedlinePlus related topics: Urine and Urination

Drug Information available for: Nifedipine BQ 123

U.S. FDA Resources

Further study details as provided by University of Edinburgh:

Primary Outcome Measures:

Proteinuria [ Time Frame: Acute change in proteinuria over 4 hour period following BQ-123 dosing ] [ Designated as safety issue: No ]
Blood pressure [ Time Frame: Acute change in blood pressure over 4 hour period following BQ-123 dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Arterial stiffness (as measured by pulse wave velocity) [ Time Frame: Acute change in arterial stiffness over 4 hour period following BQ-123 dosing ] [ Designated as safety issue: No ]
Endothelial function (as measured by flow-mediated dilatation) [ Time Frame: Acute change in endothelial function over 4 hour period following BQ-123 dosing ] [ Designated as safety issue: No ]

Enrollment:	22
Study Start Date:	May 2006
Study Completion Date:	December 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Placebo control arm of study	Drug: 0.9 % saline Single 15ml 0.9% saline infused for 15 mins as placebo control
2: Experimental 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.
3: Active Comparator Nifedipine arm of study	Drug: Nifedipine Single dose of nifedipine 10 mg given orally as active control

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00722215

Locations

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

Sponsors and Collaborators

University of Edinburgh

British Heart Foundation

Investigators

Principal Investigator:	Neeraj Dhaun, MBChB	The University of Edinburgh
Study Director:	David J Webb, MD	The University of Edinburgh

More Information

No publications provided

Responsible Party:	The University of Edinburgh ( Dr Neeraj Dhaun )
Study ID Numbers:	2006/WCRC/02, PG/05/91, 06/MRE00/12
Study First Received:	July 23, 2008
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00722215 History of Changes
Health Authority:	United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:

Endothelin antagonist
Chronic kidney disease
Proteinuria
Cardiovascular disease

Blood pressure
Arterial stiffness
Endothelial function

Study placed in the following topic categories:

Vasodilator Agents
Renal Insufficiency
Urination Disorders
Kidney Failure, Chronic
Calcium Channel Blockers
Cardiovascular Agents
Nifedipine
Signs and Symptoms

Calcium, Dietary
Proteinuria
Urologic Diseases
Renal Insufficiency, Chronic
Kidney Diseases
Cyclo(Trp-Asp-Pro-Val-Leu)
Kidney Failure

Additional relevant MeSH terms:

Vasodilator Agents
Renal Insufficiency
Molecular Mechanisms of Pharmacological Action
Urination Disorders
Physiological Effects of Drugs
Kidney Failure, Chronic
Calcium Channel Blockers
Reproductive Control Agents
Cardiovascular Agents
Nifedipine
Pharmacologic Actions

Membrane Transport Modulators
Urological Manifestations
Signs and Symptoms
Proteinuria
Tocolytic Agents
Urologic Diseases
Renal Insufficiency, Chronic
Therapeutic Uses
Kidney Diseases
Kidney Failure

ClinicalTrials.gov processed this record on September 11, 2009