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- Klinische proef NCT01283282
Investigation of the Athero-Protective Effects of Clopidogrel (APECS)
15 april 2015 bijgewerkt door: 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.
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
48
Fase
- Fase 4
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Georgia
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Atlanta, Georgia, Verenigde Staten, 30322
- Emory University Hospital
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-
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
21 jaar tot 80 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Fundamentele wetenschap
- Toewijzing: Gerandomiseerd
- Interventioneel model: Crossover-opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: Clopidogrel/Placebo
Subjects were randomized to clopidogrel 75 mg daily for 6 weeks.
Then immediately transitioned to a placebo daily for 6 weeks.
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Clopidogrel 75 mg PO qday for 6 weeks
Andere namen:
Placebo PO qday for 6 weeks
|
|
Actieve vergelijker: 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
Andere namen:
Placebo PO qday for 6 weeks
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Flow-mediated Dilation (FMD)
Tijdsspanne: 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.
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Baseline, Week 12
|
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Nitroglycerin-mediated Vasodilation
Tijdsspanne: 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.
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Baseline, Week 12
|
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Endothelial Progenitor Cells (EPCs)
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Pulse Wave Velocity (PWV)
Tijdsspanne: 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
|
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Oxidative Stress Markers
Tijdsspanne: Week 12
|
Oxidative stress was measured by using liquid chromatography to collect plasma cystine, cysteine, gluthione, and oxidized glutathione levels.
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Week 12
|
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Inflammatory Marker High-sensitivity C-reactive Protein (hsCRP)
Tijdsspanne: Week 12
|
High-sensitivity C-reactive protein (hsCRP) was measured.
The hsCRP levels were measured by Dade Behring nephelometry.
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Week 12
|
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Inflammatory Marker CD40 Ligand
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Ziyad Ghazzal, MD, American University of Beirut, Emory University
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 januari 2008
Primaire voltooiing (Werkelijk)
1 december 2010
Studie voltooiing (Werkelijk)
1 december 2010
Studieregistratiedata
Eerst ingediend
24 januari 2011
Eerst ingediend dat voldeed aan de QC-criteria
24 januari 2011
Eerst geplaatst (Schatting)
25 januari 2011
Updates van studierecords
Laatste update geplaatst (Schatting)
1 mei 2015
Laatste update ingediend die voldeed aan QC-criteria
15 april 2015
Laatst geverifieerd
1 april 2015
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Hartziekten
- Hart-en vaatziekten
- Vaatziekten
- Arteriosclerose
- Arteriële occlusieve ziekten
- Coronaire hartziekte
- Myocardiale ischemie
- Hart-en vaatziekte
- Fysiologische effecten van medicijnen
- Neurotransmitter agenten
- Moleculaire mechanismen van farmacologische werking
- Bloedplaatjesaggregatieremmers
- Purinerge P2Y-receptorantagonisten
- Purinerge P2-receptorantagonisten
- Purinerge antagonisten
- Purinerge middelen
- Clopidogrel
Andere studie-ID-nummers
- IRB00005145
- APECS (Andere identificatie: Other)
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .