Ignite Creation Date:
2024-05-05 @ 11:42 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00115583
Status:
COMPLETED
Last Update Posted:
2016-12-09
First Post:
2005-06-23
Brief Title:
The Contribution of Endothelin to Vasomotor Function in Diseased Coronary Arteries
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
The Contribution of Endothelin to Vasoreactivity in Atherosclerotic Coronary Arteries
Status:
COMPLETED
Status Verified Date:
2016-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed 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-1s 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 ie normal angiogram for the control group or onetwo 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
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-1s 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 ie normal angiogram for the control group or onetwo 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| P01HL048743 | NIH | None | httpsreporternihgovquickSearchP01HL048743 |