Johns Hopkins University, Baltimore, MD Field Center

这项申请的目标是在约翰霍普金斯大学建立一个MACH14试验的临床中心。 在推荐范围内饮酒对心血管疾病、糖尿病和相关疾病的风险的影响是 也许在酒精、营养或预防领域尚未回答的最重要的问题。 流行病学研究一直发现，酒精摄入量在推荐的限度内与 冠心病、缺血性中风和糖尿病的风险较低，但尚未进行长期随机试验 饮酒对任何慢性病风险的影响还没有进行过。直接响应PAR-16-363 (酒精对健康影响的多站点随机对照临床试验研究中心)，我们建议 全球范围内，为期六年的平衡设计随机试验，比较一种标准服务(~14 每天饮酒可减少患心血管疾病、糖尿病、死亡率和相关后果的风险 全球有7800名成年人的心血管风险高于平均水平。最大限度地提高可行性并反映实际使用 最重要的是，我们建议测试酒精消费本身是否为戒酒，从而为参与者提供 灵活选择饮料，同时使用新颖、密集但高效的方法来监控 安全。这项试验的主要具体目标是确定每天摄入14克酒精的影响。 与戒酒相比，在重大心血管事件或死亡(心肌梗死、缺血性 中风、住院心绞痛、需要血管重建术或死亡)，平均随访6年 在7,800名年龄为≥的50岁成年人中，估计10年内心血管疾病风险≥为15%或6个月前心血管疾病流行 到招生。二级目标将测试酒精对糖尿病和重大疾病风险的影响 心血管事件。三级AIMS将测试硬心血管事件和进展为受损的风险 空腹血糖。与其他大型随机试验类似，我们将在全球建立约16个中心，使用 阶梯式方法，在美国、欧洲、非洲和南部的7个中心进行为期9个月的先锋阶段 美国(在本申请中)，紧随其后的是第二波额外的网站，以完成注册。 将以多种补充方式监测参与者的安全，包括简短的电子实时 报告和验证年度仪器和实验室测量。我们高度团结在一起 美国和欧洲的成功组织建立了临床、数据和生物医学协调中心，我们的 现场中心包括许多最有经验的临床试验人员，我们的团队拥有强大的 与NIAAA和其他NIH员工建立必要的工作关系，以确保在 U10资助的合作研究努力。在这一应用中，我们提出了第一个随机临床试验 饮酒，旨在确定它是增加还是降低心血管疾病和糖尿病的风险 在全球心血管风险高于平均水平的成年人中。

This goal of this application is to establish a clinical center at Johns Hopkins University in the MACH14 trial. The effects of drinking alcohol within recommended limits on risks of CVD, diabetes, and related diseases are perhaps the most important questions yet to be answered in the fields of alcohol, nutrition, or prevention. Epidemiological studies have consistently found that alcohol intake within recommended limits is associated with lower risk of coronary heart disease, ischemic stroke, and diabetes, yet no long-term randomized trial of alcohol consumption on risk of any chronic disease has yet been performed. In direct response to PAR-16-363 (Multi-Site Randomized Controlled Clinical Trial Research Center on Alcohol's Health Effects), we propose a worldwide, six-year, balanced-design randomized trial, comparing the effects of one standard serving (~14 grams) of alcohol intake daily to abstention on risk of CVD, diabetes, mortality, and related outcomes among 7,800 adults at above-average cardiovascular risk worldwide. To maximize feasibility and reflect actual use most closely, we propose to test alcohol consumption per se to abstention and thus to offer participants flexibility in their choice of beverage, while employing novel and intensive yet efficient methods to monitor safety. The Primary Specific Aim of this trial is to determine the effects of 14 gm of alcohol intake daily compared with abstention on risk of major cardiovascular events or death (myocardial infarction, ischemic stroke, hospitalized angina, need for revascularization, or death) over an average of 6 years of follow-up among 7,800 adults aged ≥50 years with estimated 10-year CVD risk ≥15% or prevalent CVD >6 months prior to enrollment. Secondary Aims will test the effects of alcohol on risks of incident diabetes and major cardiovascular events. Tertiary Aims will test risks of hard cardiovascular events and progression to impaired fasting glucose. Similar to other large randomized trials, we will establish ~16 centers worldwide using a stepped approach, with a 9-month vanguard phase among 7 centers in the US, Europe, Africa, and South America (in this application), followed by a second wave of additional sites to complete enrollment. Participants will be monitored for safety in multiple complementary ways, including brief electronic real-time reporting and validated yearly instruments and laboratory measures. We have brought together highly successful groups in the US and Europe to establish clinical, data, and biospecimen coordinating centers, our field centers include many of the most experienced clinical trialists anywhere, and our group has strong working relationships with NIAAA and other NIH staff necessary to ensure seamless collaboration during a U10-funded cooperative research endeavor. In this application, we propose the first randomized clinical trial of alcohol consumption, aiming to determine whether it increases or decreases the risk of CVD and diabetes among adults at above-average cardiovascular risk worldwide.