Endothelin Receptor Antagonism in Proteinuric Nephropathy

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00722215
• Other study ID #: 2006/WCRC/02
• Secondary ID: PG/05/9106/MRE00
• Status: Completed
• Phase: Phase 1
• First received: July 23, 2008
• Last updated: July 23, 2008
• Start date: May 2006
• Est. completion date: December 2007

Study information

• Verified date: August 2006
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 2007
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Proteinuria
• Renal Insufficiency, Chronic

Intervention

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.
• 0.9 % saline
Single 15ml 0.9% saline infused for 15 mins as placebo control
• Nifedipine
Single dose of nifedipine 10 mg given orally as active control

Locations

Country	Name	City	State
United Kingdom	Clinical Research Centre, Western General Hospital	Edinburgh	Scotland

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	British Heart Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proteinuria		Acute change in proteinuria over 4 hour period following BQ-123 dosing	No
Primary	Blood pressure		Acute change in blood pressure over 4 hour period following BQ-123 dosing	No
Secondary	Arterial stiffness (as measured by pulse wave velocity)		Acute change in arterial stiffness over 4 hour period following BQ-123 dosing	No
Secondary	Endothelial function (as measured by flow-mediated dilatation)		Acute change in endothelial function over 4 hour period following BQ-123 dosing	No