Johns Hopkins University, Baltimore, MD Field Center

本申请的目标是在2014年试验中在约翰霍普金斯大学建立一个临床中心。 在推荐范围内饮酒对心血管疾病、糖尿病和相关疾病风险的影响是 也许是酒精、营养或预防领域中最重要的问题。 流行病学研究一致发现，在推荐范围内的酒精摄入量与 冠心病、缺血性中风和糖尿病的风险较低，但没有长期的随机试验， 酒精消费对任何慢性疾病的风险尚未进行。直接响应PAR-16-363 （酒精对健康影响的多地点随机对照临床试验研究中心），我们提出了一个 一项为期6年的全球性平衡设计随机试验，比较了一份标准服务（约14 克）的酒精摄入量，以预防心血管疾病，糖尿病，死亡率和相关结果的风险， 全球有7,800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情况 最密切的是，我们建议测试酒精消费本身，以避免，从而为参与者提供 灵活地选择饮料，同时采用新颖、密集而有效的方法来监测 安全为代价的本试验的主要具体目的是确定每天摄入14克酒精的影响 与预防主要心血管事件或死亡（心肌梗死、缺血性 卒中、住院心绞痛、需要血运重建或死亡），平均随访6年 在7，800名年龄≥50岁的成人中，估计10年CVD风险≥15%或既往CVD患病率>6个月 到注册。次要目的将测试酒精对糖尿病发病风险的影响， 心血管事件。三级目标将检测严重心血管事件和进展至受损的风险 空腹血糖与其他大型随机试验类似，我们将在全球范围内建立约16个中心， 分阶段进行，在美国、欧洲、非洲和南部的7个中心中进行为期9个月的先锋阶段 美国（在本申请中），然后是第二波额外的研究中心完成入组。 将以多种补充方式监测参与者的安全性，包括简短的电子实时 报告和验证年度仪器和实验室测量。我们聚集在一起， 在美国和欧洲的成功团体建立临床，数据和生物标本协调中心，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工作人员建立必要的工作关系，以确保在 U10资助的合作研究奋进。在这项申请中，我们提出了第一个随机临床试验， 酒精消费，旨在确定它是否增加或减少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.