Endothelin Receptor Antagonism in Proteinuric Nephropathy
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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 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Basic Science |
| Official Title: | The Systemic & Renal Effects of Endothelin Receptor Antagonism in Proteinuric Nephropathy |
- 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 ]
- 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 |
|---|---|
|
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 Name: Adalat
|
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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00722215
| United Kingdom | |
| Clinical Research Centre, Western General Hospital | |
| Edinburgh, Scotland, United Kingdom, EH4 2XU | |
| 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: | Dr Neeraj Dhaun, The University of Edinburgh |
| ClinicalTrials.gov Identifier: | NCT00722215 History of Changes |
| Other Study ID Numbers: | 2006/WCRC/02, PG/05/91, 06/MRE00/12 |
| Study First Received: | July 23, 2008 |
| Last Updated: | July 23, 2008 |
| 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 |
Additional relevant MeSH terms:
|
Kidney Diseases Renal Insufficiency, Chronic Renal Insufficiency Urologic Diseases |
ClinicalTrials.gov processed this record on February 27, 2015