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

15 aprile 2015 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Intervento / Trattamento

Descrizione dettagliata

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 di studio

Interventistico

Iscrizione (Effettivo)

48

Fase

  • Fase 4

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • Georgia
      • Atlanta, Georgia, Stati Uniti, 30322
        • Emory University Hospital

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 21 anni a 80 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione incrociata
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: 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
Altri nomi:
  • Plavix
Placebo PO qday for 6 weeks
Comparatore attivo: 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
Altri nomi:
  • Plavix
Placebo PO qday for 6 weeks

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Flow-mediated Dilation (FMD)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Pulse Wave Velocity (PWV)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

  • Investigatore principale: Ziyad Ghazzal, MD, American University of Beirut, Emory University

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 gennaio 2008

Completamento primario (Effettivo)

1 dicembre 2010

Completamento dello studio (Effettivo)

1 dicembre 2010

Date di iscrizione allo studio

Primo inviato

24 gennaio 2011

Primo inviato che soddisfa i criteri di controllo qualità

24 gennaio 2011

Primo Inserito (Stima)

25 gennaio 2011

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

1 maggio 2015

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 aprile 2015

Ultimo verificato

1 aprile 2015

Maggiori informazioni

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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