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|---|---|---|---|
| APECS | Other Identifier | Other |
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The investigators would like to investigate whether clopidogrel will help lower the level of harmful markers in patients with coronary artery disease, and at the same time will help increase the cells that are useful in repairing the damaged blood vessels. The investigators will give half of the patients clopidogrel and the other half a sugar pill, placebo, and check the levels of these markers and helpful cells in each group. At the same time the investigators will check how well these patient's blood vessels work using ultrasound imaging of the forearm to see how blood vessels relax and tonometry to see how stiff the patient's blood vessels are. After 6 weeks of drug therapy, the patients will switch to the other drug and these same tests will be performed after an additional 6 weeks of therapy. The drug taken by the patient will not be known to the patient or the researchers. The patients will continue on their prescribed medical therapy during the duration of the 12 week study.
Blockages in the blood vessels of the heart are caused by atherosclerosis. Atherosclerosis is the main cause for chest pain and heart attacks. Gradual narrowing of the vessels of the heart caused by blockages causes chronic symptoms, such as chest pain. Those with these findings often have a cardiac catheterization to detect these blockages. Additionally these patients may have an angioplasty or stent placed to help relieve these symptoms. With this angioplasty/stent procedure, patients are placed on the drug clopidogrel to help prevent clots from forming and narrowing of the blood vessels. Clopidogrel is a blood thinner that prevents clots from forming similar to an aspirin, but is more powerful and effective. Markers, or substances, have been identified that cause worsening of the blockages in the blood vessels of the heart. Many of these substances have been shown to decrease with the use of clopidogrel. This occurs separately from clopidogrel's ability to prevent clots. Endothelial progenitor cells, or EPCs, come mostly from the bone marrow and is helpful in repairing damage to the lining of the blood vessels of the heart. The EPCs help balance out the damage incurred in the blood vessels from those harmful markers. Several other drugs commonly used in heart disease have recently been shown to improve EPCs function. With this in mind, it is important to understand more of clopidogrel's function. A decrease in markers that cause worsening of the blockages, and an increase in the number of cells that will help repair damaged blood vessels of the heart is important in avoiding future chest pain and heart attacks. This may be how clopidogrel is currently protecting patients from developing new blockages. The investigators would like to investigate whether clopidogrel will help lower the level of harmful markers in patients with coronary artery disease, and at the same time will help increase the cells that are useful in repairing the damaged blood vessels. The investigators will give half of the patients clopidogrel and the other half a sugar pill, placebo, and check the levels of these markers and helpful cells in each group. At the same time the investigators will check how well these patient's blood vessels work using ultrasound imaging of the forearm to see how blood vessels relax and tonometry to see how stiff the patient's blood vessels are. After 6 weeks of drug therapy, the patients will switch to the other drug and these same tests will be performed after an additional 6 weeks of therapy. The drug taken by the patient will not be known to the patient or the researchers. The patients will continue on their prescribed medical therapy during the duration of the 12 week study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clopidogrel/Placebo | Active Comparator | Subjects were randomized to clopidogrel 75 mg daily for 6 weeks. Then immediately transitioned to a placebo daily for 6 weeks. |
|
| Placebo/Clopidogrel | Active Comparator | Subjects were randomized to a placebo daily for 6 weeks. Then immediately transitioned to clopidogrel 75 mg daily for 6 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clopidogrel | Drug | Clopidogrel 75 mg PO qday for 6 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Flow-mediated Dilation (FMD) | Flow-mediated dilation (FMD) collected by an ultrasound and is measured by the percent change in diameter of the brachial artery from baseline to 12 weeks. | Baseline, Week 12 |
| Nitroglycerin-mediated Vasodilation | Nitroglycerin (NTG)-mediated vasodilation was measured after 0.4 mg of NTG was administered sublingually. Brachial artery images were obtained via ultrasound after three minutes of NTG administration. Measurements from the twelve frames will be averaged to calculate the percent change in diameter of the brachial artery from baseline to 12 weeks. | Baseline, Week 12 |
| Endothelial Progenitor Cells (EPCs) | The circulating progenitor-enriched population of cells was measured by the expression of surface antigens using direct flow cytometry for CD34+, CD34+/CD133+, CD34+/ VEGF2R+ and CD34+/CD133+/VEGF2R+ | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Pulse Wave Velocity (PWV) | PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in seconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually. | Week 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Arshed A Quyyumi, MD | Emory University | Principal Investigator |
| Ziyad Ghazzal, MD | American University of Beirut, Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University Hospital | Atlanta | Georgia | 30322 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24336012 | Derived | Ramadan R, Dhawan SS, Syed H, Pohlel FK, Binongo JN, Ghazzal ZB, Quyyumi AA. Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease. J Cardiovasc Pharmacol. 2014 Apr;63(4):369-74. doi: 10.1097/FJC.0000000000000057. |
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Patients recruited from clinic sites at Emory University Hospital, Crawford Long Hospital, Grady Memorial Hospital and VA Medical Center between January 2008 through December 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo First/Then Clopidogrel | The subjects received placebo PO qd for the first 6 weeks then were switched to clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between. |
| FG001 | Clopidogrel First/Then Placebo | The subjects received clopidogrel 75 mg PO qd for the first 6 weeks then were switched to placebo PO qd therapy for an additional 6 weeks without any wash out period in between. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (6 Weeks) |
|
| |||||||||||||||||||||
| Second Intervention (6 Weeks) |
|
41 subjects completed the entire study.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects | The subjects received clopidogrel 75 mg or placebo PO qd for the first 6 weeks then were switched to receive either placebo or clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Flow-mediated Dilation (FMD) | Flow-mediated dilation (FMD) collected by an ultrasound and is measured by the percent change in diameter of the brachial artery from baseline to 12 weeks. | Posted | Mean | Standard Error | percent change in diameter | Baseline, Week 12 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Clopidogrel | The subjects received clopidogrel 75 mg or placebo PO qd for the first 6 weeks then were switched to receive either placebo or clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between. |
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Limited sample size
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Arshed Quyyumi | Emory University | 404-727-3655 | aquyyum@emory.edu |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
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| Placebo | Drug | Placebo PO qday for 6 weeks |
|
| Oxidative Stress Markers | Oxidative stress was measured by using liquid chromatography to collect plasma cystine, cysteine, gluthione, and oxidized glutathione levels. | Week 12 |
| Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP) | High-sensitivity C-reactive protein (hsCRP) was measured. The hsCRP levels were measured by Dade Behring nephelometry. | Week 12 |
| Inflammatory Marker CD40 Ligand | CD40 ligand levels were measured. The level of CD40 ligand were measured using the Flurokine MultiAnalyte profiling (MAP) Human Base Kit B. | Week 12 |
| Lost to Follow-up |
|
| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Nitroglycerin-mediated Vasodilation | Nitroglycerin (NTG)-mediated vasodilation was measured after 0.4 mg of NTG was administered sublingually. Brachial artery images were obtained via ultrasound after three minutes of NTG administration. Measurements from the twelve frames will be averaged to calculate the percent change in diameter of the brachial artery from baseline to 12 weeks. | Posted | Mean | Standard Error | percent change in diameter | Baseline, Week 12 |
|
|
|
| Primary | Endothelial Progenitor Cells (EPCs) | The circulating progenitor-enriched population of cells was measured by the expression of surface antigens using direct flow cytometry for CD34+, CD34+/CD133+, CD34+/ VEGF2R+ and CD34+/CD133+/VEGF2R+ | Posted | Mean | Standard Error | cells/µL | Week 12 |
|
|
|
| Secondary | Pulse Wave Velocity (PWV) | PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in seconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually. | Posted | Mean | Standard Error | m/s | Week 12 |
|
|
|
| Secondary | Oxidative Stress Markers | Oxidative stress was measured by using liquid chromatography to collect plasma cystine, cysteine, gluthione, and oxidized glutathione levels. | Posted | Mean | Standard Error | µM | Week 12 |
|
|
|
| Secondary | Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP) | High-sensitivity C-reactive protein (hsCRP) was measured. The hsCRP levels were measured by Dade Behring nephelometry. | Posted | Mean | Standard Error | mg/L | Week 12 |
|
|
|
| Secondary | Inflammatory Marker CD40 Ligand | CD40 ligand levels were measured. The level of CD40 ligand were measured using the Flurokine MultiAnalyte profiling (MAP) Human Base Kit B. | Posted | Mean | Standard Error | pg/mL | Week 12 |
|
|
|
| 0 |
| 48 |
| 0 |
| 48 |
| EG001 | Placebo | The subjects received clopidogrel 75 mg or placebo PO qd for the first 6 weeks then were switched to receive either placebo or clopidogrel 75 mg PO qd therapy for an additional 6 weeks without any wash out period in between. | 0 | 48 | 0 | 48 |
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| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D009930 |
| Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| CD34+/VEGF2R+ |
|
| CD34+/CD133+/VEGF2R+ |
|
| Glutathione |
|
| Oxidized glutathione |
|