Clinical Trials Logo

Clinical Trial Summary

The purpose of the study is to assess the importance of a substance called endothelin. Endothelin is produced by coronary arteries. This study examines this substance to determine whether it has an effect on controlling blood flow in coronary arteries. When these arteries release too much endothelin, the blood flow to the heart muscle is reduced and this may be important in heart conditions. This protocol examines an investigational drug called BQ-123 to see if it blocks the effect of endothelin. We assess the blood flow in the coronaries and evaluate the effects of BQ-123. It is anticipated that this endothelin blocker will open up coronary arteries and increase the blood flow to the heart.


Clinical Trial Description

There are many substances that influence the diameter of the coronary artery and a number of these are actually released by the lining of the coronary arteries (referred to as the endothelium). Over the past 15 years, our laboratory has been instrumental in establishing the role of endothelium-released relaxing factors which relax (open) the coronary arteries. We are now focussing our attention on factors which constrict the coronary artery, in particular a substance called endothelin-1 (ET-1). This potent constrictor substance has been found to accumulate at coronary artery sites which may produce unstable angina (ie the culprit lesion or stenosis). Hence ET-1 may produce localized constriction of a coronary stenosis thereby further narrowing the remaining lumen and cutting off blood flow to the heart muscle and thus leading to unstable angina.

If ET-1 is important in the development of unstable angina, then medications which inhibit the effects of ET-1 should improve the condition. To achieve a blockade of ET-1, inhibitors of the two receptors (ET-A and ET-B) responsible for ET-1's action must be administered. Animal and human studies have demonstrated that a blockade of the ET-A receptor by the new antagonist, BQ-123, inhibits most of the ET-1 induced constrictor response. BQ-123 has been safely administered systemically by intravenous infusion and locally in the human forearm where it produces dilation of the forearm arteries. It has not been previously administered into human coronary arteries.

Consented patients whose routine diagnostic angiogram shows suitable anatomy (i.e., normal angiogram for the control group, or one/two vessel coronary artery disease with an identifiable culprit stenosis) will have placement of a coronary artery angiographic catheter. Placement of this catheter does not require an additional puncture of an artery (already performed in the routine diagnostic angiogram).

The angiographic catheter allows visualization of the internal diameter of the coronary arteries by the injection of a radiographic contrast with the image being recorded on a cine film. Specialized imaging machines will measure the diameter of the vessel.

Through the angiographic catheter, an infusion catheter (by which the drugs can be administered) and a coronary Doppler flow wire are placed in the coronary artery. The latter instrument is a well-established tool for measuring coronary blood flow.

After establishing baseline values for heart rate, blood pressure, culprit stenosis internal diameter and coronary blood flow, the following sequential intracoronary infusions will be undertaken:

1. Infusion of the endothelin antagonist, BQ-123, over a 60 minute period. This inhibitor requires up to 60 minutes exerting a full effect;

2. Adenosine bolus injection, to assess the vasodilation capacity of the small coronary arteries; and

3. Nitroglycerin bolus injection, to assess the maximal vasodilation capacity of the large coronary arteries.

At 5, 15, 30, 45, and 60 minutes of endothelin antagonist infusion, and immediately after the bolus injections, the above parameters will be reassessed. It is anticipated that this research protocol will be completed within 90 minutes.

Following the research protocol, the patient will undergo appropriate coronary intervention as dictated by the clinical situation. If coronary atherectomy is required for clinical indications, then the specimen extracted by this procedure will be sent for specific analysis of endothelin-1 content. A correlation between the amount of endothelin at the culprit stenosis and the response to the endothelin antagonist can then be examined. In cardiac transplant recipients, endomyocardial biopsies are also routinely obtained for clinical purposes at the time of catheterization. One of these specimens will be used for ET-1 immunoreactivity analysis. A total of 2 teaspoons of blood will be taken and frozen for analysis. ;


Study Design

Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label


Related Conditions & MeSH terms


NCT number NCT00115583
Study type Interventional
Source Brigham and Women's Hospital
Contact
Status Completed
Phase N/A
Start date November 1998
Completion date April 2007

See also
  Status Clinical Trial Phase
Recruiting NCT03427996 - Evaluation of Effectiveness and Safety of Rotational Atherectomy in Routine Clinical Practice
Not yet recruiting NCT04762472 - Air Pollution (PM2.5) on Accelerated Atherosclerosis: A Montelukast Interventional Study in Modernizing China Phase 4
Not yet recruiting NCT03174418 - Fluid-dynamics in Bifurcation PCI N/A
Not yet recruiting NCT03813017 - Comprehensive Assessment of Subclinical Atherosclerosis in Patients With Rheumatoid Arthritis
Recruiting NCT05600088 - Intracoronary Cryotherapy Effect on Stabilization of Vulnerable Plaque in Patients With NSTEMI or Unstable Angina N/A
Completed NCT03011775 - Effect of Pioglitazone on Insulin Resistance, Atherosclerosis Progression and Clinical Course of Coronary Heart Disease Phase 4
Completed NCT03149042 - Validation of a Computed Tomography (CT) Based Fractional Flow Reserve (FFR) Software Using the 320 Detector Aquilion ONE CT Scanner.
Not yet recruiting NCT05540223 - Safety and Clinical Performance of the DREAMS 3G Resorbable Magnesium Scaffold System N/A
Completed NCT02389946 - Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions N/A
Completed NCT01234870 - Comprehensive Evaluation of Ischemic Heart Disease Using MRI Phase 2/Phase 3
Completed NCT03471611 - Study of Intracoronary CD34+ Cell Administration in Patients With Early Coronary Atherosclerosis Phase 1
Completed NCT00353795 - Coronary Atherosclerosis Evaluation by Arterial Wall Magnetic Resonance Imaging (MRI) N/A
Enrolling by invitation NCT04810364 - HIV Infection And Evolvement of Atherosclerotic Plaque
Active, not recruiting NCT04175626 - Safety and Effectiveness of the Orsiro Sirolimus Eluting Coronary Stent System in Subjects With Coronary Artery Lesions
Recruiting NCT00146887 - Comparison of Coronary CT Angiography to Invasive Coronary Angiography N/A
Completed NCT05492084 - Personalized Risk of Rapidly Progressive Atherosclerosis
Recruiting NCT04853511 - Comprehensive Assessment of Interconnection Between Brain Emotional Activity and Coronary Plaque Instability
Completed NCT03815032 - Assessing the Accuracy of the OptoWire DeuxTM in a Wire to Wire Comparison N/A
Active, not recruiting NCT03129503 - Optical Coherence Tomography in Acute Coronary Syndrome
Recruiting NCT06393894 - Latvian Early Atherosclerosis Registry