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Investigation of the Athero-Protective Effects of Clopidogrel (APECS)

15 de abril de 2015 actualizado por: Arshed A. Quyyumi, Emory University

Phase 4 Study of Clopidogrel in Patients With Stable Coronary Artery Disease to Determine Effects on Vascular Function, Biomarkers and Endothelial Progrenitor Cells

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.

Descripción general del estudio

Estado

Terminado

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

48

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Emory University Hospital

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

21 años a 80 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Male or females without child bearing potential aged 21-80 years
  • Known coronary artery disease by angiogram or documented myocardial infarction.
  • Able to provide written informed consent

Exclusion Criteria:

  • Treated with clopidogrel or ticlodipine in the previous 3 months
  • Age < 21 or >80 years
  • Premenopausal females with potential for pregnancy
  • Allergy to clopidogrel or aspirin
  • Initiation or change in dose of any concomitant medical therapy within 2 months before the study
  • Uncontrolled hypertension with BP>180 mmHg systolic and >120 mmHg diastolic
  • Treated with coumadin therapy
  • Intolerance or allergy to statins
  • Acute infection in previous 4 weeks
  • History of substance abuse
  • Uninterpretable PAT test
  • Current neoplasm
  • Chronic renal failure [creatinine > 2.5 mg/dL] or liver failure (Liver enzymes >2X normal)
  • Acute coronary syndrome, heart failure, CVA, coronary intervention within 3 months
  • Known aortic stenosis, hypertrophic cardiomyopathy, symptomatic heart failure.
  • Inability to give informed consent
  • Inability to return to Emory for follow-up

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Ciencia básica
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación cruzada
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Clopidogrel/Placebo
Subjects were randomized to clopidogrel 75 mg daily for 6 weeks. Then immediately transitioned to a placebo daily for 6 weeks.
Clopidogrel 75 mg PO qday for 6 weeks
Otros nombres:
  • Plavix
Placebo PO qday for 6 weeks
Comparador activo: Placebo/Clopidogrel
Subjects were randomized to a placebo daily for 6 weeks. Then immediately transitioned to clopidogrel 75 mg daily for 6 weeks.
Clopidogrel 75 mg PO qday for 6 weeks
Otros nombres:
  • Plavix
Placebo PO qday for 6 weeks

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Flow-mediated Dilation (FMD)
Periodo de tiempo: Baseline, Week 12
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
Periodo de tiempo: Baseline, Week 12
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)
Periodo de tiempo: Week 12
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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pulse Wave Velocity (PWV)
Periodo de tiempo: Week 12
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
Oxidative Stress Markers
Periodo de tiempo: Week 12
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)
Periodo de tiempo: Week 12
High-sensitivity C-reactive protein (hsCRP) was measured. The hsCRP levels were measured by Dade Behring nephelometry.
Week 12
Inflammatory Marker CD40 Ligand
Periodo de tiempo: Week 12
CD40 ligand levels were measured. The level of CD40 ligand were measured using the Flurokine MultiAnalyte profiling (MAP) Human Base Kit B.
Week 12

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Investigadores

  • Investigador principal: Ziyad Ghazzal, MD, American University of Beirut, Emory University

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de enero de 2008

Finalización primaria (Actual)

1 de diciembre de 2010

Finalización del estudio (Actual)

1 de diciembre de 2010

Fechas de registro del estudio

Enviado por primera vez

24 de enero de 2011

Primero enviado que cumplió con los criterios de control de calidad

24 de enero de 2011

Publicado por primera vez (Estimar)

25 de enero de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

1 de mayo de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

15 de abril de 2015

Última verificación

1 de abril de 2015

Más información

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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