Endothelin Receptor Antagonism in Proteinuric Nephropathy
|Chronic Kidney Disease Proteinuria||Drug: BQ-123 (selective endothelin A receptor antagonist) Drug: 0.9 % saline Drug: Nifedipine||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, 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 ]
- Blood pressure [ Time Frame: Acute change in blood pressure over 4 hour period following BQ-123 dosing ]
- Arterial stiffness (as measured by pulse wave velocity) [ Time Frame: 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 ]
|Study Start Date:||May 2006|
|Study Completion Date:||December 2007|
|Primary Completion Date:||November 2007 (Final data collection date for primary outcome measure)|
Placebo Comparator: 1
Placebo control arm of study
Drug: 0.9 % saline
Single 15ml 0.9% saline infused for 15 mins as placebo control
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
Single dose of nifedipine 10 mg given orally as active control
Other Name: Adalat
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00722215
|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|