Enrichment of CES1 Carriers in the Pharmacogenomics Anti-Platelet Intervention Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Changes in Platelet Function in Response to Clopidogrel
研究概览
简要总结
This study builds, in part, upon preliminary results generated as part of the Pharmacogenomics Anti-Platelet Intervention (PAPI) Study (NCT00799396). The purpose of this investigation is to assess the impact of genetic variation in the carboxylesterase 1 (CES1) on response to clopidogrel as well as dual antiplatelet therapy (i.e. clopidogrel and aspirin), as assessed by ex vivo platelet aggregometry, in healthy Amish individuals. The investigators hypothesize that participants who carry alleles that modify the activity or expression of CES1 will have altered response to clopidogrel as well as dual antiplatelet therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 20 years or older
- •Of Old Order Amish descent
排除标准
- •Currently pregnant or less than 6 months have passed since delivery
- •Currently breast feeding
- •Has a history of a bleeding disorder or major spontaneous bleed, such as peptic ulcer, epistasis, or intracranial bleed
- •Has severe hypertension, defined by a blood pressure above 160/95 mm Hg
- •Takes medications that would affect the outcome(s) to be measured and cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation
- •Is taking vitamins or other supplements and is unwilling to discontinue use for at least 1 week prior to study
- •Has a coexisting malignancy
- •Has a creatinine level greater than 2.0 mg/dl, aspartate transaminase (AST) or alanine transaminase (ALT) greater than two times the upper limit of normal, hematocrit less than 32%, or a thyroid-stimulating hormone (TSH) less than 0.4 or greater than 5.5 mIU/L
- •Has a bleeding disorder or history of gastrointestinal bleeding or other major bleeding episode
- •Is currently taking aspirin, clopidogrel, or anti-coagulants, such as warfarin, heparin, or GPIIb/IIIa antagonists, and have conditions that might place the participant at increased risk from withdrawal of these medications 14 days prior to protocol initiation
- •History of unstable angina, heart attack, angioplasty (including stent placement), coronary artery bypass surgery, atrial fibrillation, stroke or transient ischemic attacks, diabetes, or deep vein thrombosis or other thrombosis
- •Has polycythemia, or thrombocytosis, defined by a platelet count greater than 500,000
- •Has thrombocytopenia, defined by a platelet count less than 75,000
- •Has had surgery within the last 6 months
- •Has an aspirin or clopidogrel allergy
研究组 & 干预措施
Overall Cohort
Participants will receive clopidogrel treatment alone (300 mg loading dose followed by 75 mg/d for 6 days), followed by clopidogrel (75 mg) plus aspirin (324 mg) treatment on day 8.
干预措施: Aspirin (Drug)
Overall Cohort
Participants will receive clopidogrel treatment alone (300 mg loading dose followed by 75 mg/d for 6 days), followed by clopidogrel (75 mg) plus aspirin (324 mg) treatment on day 8.
干预措施: Clopidogrel (Drug)
结局指标
主要结局
Changes in Platelet Function in Response to Clopidogrel
时间窗: Measured at baseline and after 8 days of clopidogrel treatment
Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation in response to ADP (20 ug/ml) or collagen (5 ug/ml). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline (recorded as a percentage) minus the maximum platelet aggregation value obtained after clopidogrel administration but before aspirin administration (also recorded as percentage). Thus, values recorded below represent a percentage change.
Changes in Platelet Function in Response to Clopidogrel Plus Aspirin
时间窗: Measured at baseline and after 8 days clopidogrel administration plus 1 day of aspirin treatment
Baseline minus post clopidogrel/post-aspirin platelet rich plasma (PRP) maximum aggregation in response to ADP (20 ug/ml) or collagen (5 ug/ml). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline (recorded as a percentage) minus the maximum platelet aggregation value obtained after clopidogrel and aspirin administration (also recorded as percentage). Thus, values recorded below represent a percentage change.
次要结局
未报告次要终点
研究者
Braxton Mitchell
Professor of Medicine
University of Maryland, Baltimore