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NCT Number: NCT00722215

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.

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Key information

Conditions

Chronic Kidney Disease Cardiovascular Diseases Chronic Disease Disease Attributes Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Kidney Diseases Male Urogenital Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Proteinuria Renal Insufficiency Renal Insufficiency, Chronic Signs and Symptoms Urination Disorders Urogenital Diseases Urologic Diseases Urological Manifestations

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Clinical Research Centre, Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BQ-123 (selective endothelin A receptor antagonist)

Drug

Single dose of BQ-123 given at a dose of 1000 nmol/min for 15 min intravenously.

0.9 % saline

Drug

Single 15ml 0.9% saline infused for 15 mins as placebo control

nifedipine

Drug

Single dose of nifedipine 10 mg given orally as active control

Other names: Adalat

Primary outcomes

  1. Proteinuria

    Time frame: Acute change in proteinuria over 4 hour period following BQ-123 dosing

  2. Blood pressure

    Time frame: Acute change in blood pressure over 4 hour period following BQ-123 dosing

Secondary outcomes

  1. Arterial stiffness (as measured by pulse wave velocity)

    Time frame: Acute change in arterial stiffness over 4 hour period following BQ-123 dosing

  2. Endothelial function (as measured by flow-mediated dilatation)

    Time frame: Acute change in endothelial function over 4 hour period following BQ-123 dosing

Sponsors and collaborators

Lead sponsor

University of Edinburgh

Other

Collaborators

  • British Heart Foundation

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2007
Study completion
2007
First posted
Jul 25, 2008
Registry last updated
Jul 25, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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