Planning Grant for a Multi Center RCT of Moderate Alcohol Use on Chronic Disease

适度饮酒治疗慢性病的多中心随机对照试验计划拨款

• 批准号: 8757476
• 负责人: KENNETH Jay MUKAMAL
• 金额: $ 46.96万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-20 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8757476
• 关键词: Accidents; Adherence; Adult; Affect; Africa; Alcohol abuse; Alcohol consumption; Alcoholism; Alcohols; Animals; Area; Asia; Atherosclerosis; Benefits and Risks; Beverages; Biological; Bone Density; Breast; Cardiovascular Diseases; Cardiovascular system; Cholelithiasis; Chronic Disease; Clinical; Clinical Trials; Clinical Trials Design; Clinical trial protocol document; Collaborations; Congestive Heart Failure; Coronary heart disease; Data; Development; Development Plans; Diabetes Mellitus; Disease; Documentation; Effectiveness; Elderly; Ensure; Epidemiologic Studies; Epidemiologist; Equilibrium; Estrogen Therapy; Estrogens; Ethanol; Europe; Face; Fibrinogen; Fracture; Future; Goals; Gold; Grant; Health; Health Care Seeking Behavior; Health Status; High Density Lipoprotein Cholesterol; Human; Hypertension; Influentials; Institutional Review Boards; Insulin Resistance; Intake; International; Intervention; Ischemic Stroke; Link; Malignant Neoplasms; Manuals; Methods; Monitor; Myocardial Infarction; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; North America; Nutritional; Observational Study; Outcome; Outpatients; Participant; Pathway interactions; Patients; Pattern; Phase; Physicians; Postmenopause; Preparation; Protocols documentation; Psychiatrist; Randomized; Randomized Clinical Trials; Recommendation; Recruitment Activity; Research Infrastructure; Research Personnel; Residual state; Risk; Safety; Scientist; Site; Specimen; Stroke; Testing; Trauma; U-Series Cooperative Agreements; Woman; Women' s Health; Work; adiponectin; adjudicate; alcohol epidemiology; alcohol risk; cardiovascular disorder risk; cardiovascular risk factor; clinical practice; clinical research site; cost; data management; design; disorder prevention; drinking; experience; feeding; high risk drinking; improved; international center; malignant breast neoplasm; meetings; men; middle age; mortality; novel; operation; preference; public health relevance; randomized trial; repository; research study; response; sex; success

DESCRIPTION (provided by applicant): Moderate or low-risk alcohol consumption (defined by NIAAA as d4 drinks on any single day AND d14 drinks per week for men or d3 drinks on any single day AND d7 drinks per week for non-pregnant women) has been associated - despite its appellation - with a wide variety of health outcomes of the greatest import. Compared with abstainers or rare drinkers, moderate drinkers have been observed to have lower rates of coronary heart disease, congestive heart failure, ischemic stroke, diabetes, and cholelithiasis but higher rates of breast and possibly other cancers; relationships with fractures are less certain, although evidence suggests that moderate alcohol may simultaneously raise risk of trauma yet improve bone density. Perhaps most compellingly, moderate alcohol intake has been associated with a lower risk of all-cause mortality, chiefly reflecting its inverse associatio with cardiovascular mortality. Important limitations affect this body of evidence, however. Although large and consistent epidemiological studies have been conducted, strong concerns about residual confounding by both health status and health- seeking behavior exist. The existing experimental studies of alcohol are small and short and, while demonstrating plausible mechanisms by which moderate drinking would lower cardiometabolic risk, the lack of correspondence between similar studies of postmenopausal estrogen treatment and the randomized Women's Health Initiative clinical trial only heightens this concern. Given the widespread use of alcohol, the clear risks and costs of its overuse, the uncertain balance of risks and benefits of moderate use, and the complete lack of definitive clinical trial data, the urgent need for a clinical trial of moderate alcohol intake is unmistakable. In this Clinical Trial Planning Cooperative Agreement (U34) application, we propose to develop a multi-center, international, long-term, pragmatic randomized clinical trial of moderate drinking on the key clinical outcomes with which it has been associated - cardiovascular disease, cancer, diabetes, trauma, accidents, mortality, and progression to heavy or at-risk drinking. Building upon a team of established investigators and field centers with clinical trial and/or alcohol expertise (both i most cases) in North America, Asia, Europe, and Africa, we intend to develop a clinical trial protocol, recruit additional field centers, establish a data management network, and outline practical strategies for recruitment, intervention, monitoring, and outcome ascertainment across diverse settings. With a focus upon adults at higher cardiovascular risk to maximize efficiency, we will partner with NIAAA to develop a definitive clinical trial that can provide patients and clinicians worldwide with gold- standard advice about the effectiveness of moderate drinking in chronic disease prevention.

描述（由申请人提供）：中度或低风险的酒精消费（NIAAA定义为男性每天饮用4杯，每周饮用14杯或非孕妇每天饮用3杯，每周饮用7杯）与各种最重要的健康结果相关-尽管其名称。与不饮酒者或很少饮酒者相比，适度饮酒者冠心病、充血性心力衰竭、缺血性中风、糖尿病和胆石症的发病率较低，但乳腺癌和其他癌症的发病率较高；尽管有证据表明，适度饮酒可能同时增加创伤风险，但与骨折的关系尚不确定。也许最令人信服的是，适度饮酒与全因死亡风险较低有关，主要反映了其与心血管疾病死亡率呈负相关。然而，重要的局限性影响了这一证据体系。虽然已经进行了大规模和一致的流行病学研究，但对健康状况和寻求健康行为的残留混淆仍然存在强烈的担忧。现有的关于酒精的实验研究规模小且时间短，虽然证明了适度饮酒会降低心脏代谢风险的合理机制，但绝经后雌激素治疗的类似研究与随机妇女健康倡议临床试验之间缺乏对应关系，这只会加剧这种担忧。鉴于酒精的广泛使用，其过度使用的明显风险和成本，适度使用的风险和益处的不确定平衡，以及完全缺乏明确的临床试验数据，迫切需要进行适度饮酒的临床试验是毋庸置疑的。在这个临床试验中