VITAMIN D STUDY

维生素 D 研究

• 批准号: 8359894
• 负责人: Gary H Gibbons
• 金额: $ 16.63万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359894
• 关键词: Adult; African American; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cholecalciferol; Clinical; Clinical Research; Diabetes Mellitus; Disease; Dose; Double-Blind Method; Event; Functional disorder; Funding; Grant; Human; Hypertension; Intervention; Lead; Link; Mediator of activation protein; Metabolic Pathway; Molecular; National Center for Research Resources; Obesity; Outcome; Overweight; Pathway interactions; Placebo Control; Placebos; Population; Population Heterogeneity; Positioning Attribute; Principal Investigator; Public Health; Randomized; Research; Research Infrastructure; Resources; Source; Subgroup; Therapeutic; Therapeutic Agents; Therapeutic Effect; Translating; Translational Research; United States National Institutes of Health; Vitamin D; Vitamin Deficiency; Work; cardiovascular risk factor; cost; ethnic minority population; evidence base; mortality; pilot trial

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cardiovascular Disease (CVD) and related disorders remain the leading cause of death in the nation . Hypovitaminosis D has been linked not only to several cardiovascular (CV) risk factors including hypertension, diabetes, obesity , , but also to increased rates of CVD. Thus, hypovitaminosis D presents a common pathway for a select subgroup with a clustering of CV risk factors in a profile that is predominant among ethnic minorities. Indeed, hypovitaminosis D is highly prevalent with an estimated 55% of the US adult population having levels at or below 30 ng/ml, and over 80% of African Americans having suboptimal values. A large body of evidence supports the premise that therapeutic agents that have salutary effects on vascular function, often translate into therapeutic benefits on 'harder' clinical endpoints such as adverse CV events and mortality. Exploring the potential vascular effects of vitamin D repletion presents a unique opportunity to examine both clinical outcomes and specific mechanistic pathways of a potentially modifiable intervention that could result in significant impact at a public health level. Thus, we propose a twelve week randomized double-blind, placebo controlled pilot trial to assess the effect on vascular function and CV risk factors of 100,000 IU Vitamin D3 given every 4 weeks to overweight, hypertensive African-Americans with hypovitaminosis D. To our knowledge, the proposed project is the first to assess the effect of 'high-dose' Vitamin D3 administration on vascular function. We believe this study is also the first to examine the impact at a molecular level of Vitamin D3 repletion on the key mediators of cardio-metabolic pathways in humans. If our study results support our working hypothesis, we will be positioned to propose a larger scale study to detect a therapeutic effect on more definitive, clinical cardiovascular endpoints across a more diverse population. Hypothesis: Hypovitaminosis D activates select vasconstrictive and hypertrophic mediators that lead to endothelial dysfunction, elevated blood pressure and CVD; and Vitamin D3 repletion (using evidenced-based repletion strategies), in comparison to placebo, will ameliorate these abnormalities.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 心血管疾病(CVD)和相关疾病仍然是该国主要的死亡原因。维生素D缺乏不仅与高血压、糖尿病、肥胖等几种心血管(CV)危险因素有关，还与心血管疾病发病率增加有关。因此，维生素D缺乏症代表了一种共同的途径，即在少数族裔中占主导地位的特定亚组的心血管危险因素聚集。事实上，维生素D缺乏症非常普遍，据估计，55%的美国成年人口的维生素D水平低于或低于30 ng/ml，超过80%的非裔美国人的水平低于最佳值。 大量证据支持这样的假设，即对血管功能有有益影响的治疗剂，通常会转化为对“较难”的临床终点的治疗益处，如不良心血管事件和死亡率。探索维生素D补充对血管的潜在影响提供了一个独特的机会，可以研究潜在的可修改干预的临床结果和特定的机制途径，这种干预可能会对公共卫生水平产生重大影响。因此，我们提出了一项为期12周的随机、双盲、安慰剂对照的初步试验，以评估每4周给予100,000国际单位维生素D3对超重、高血压、维生素D缺乏的非洲裔美国人血管功能和心血管危险因素的影响。据我们所知，该项目是第一次评估大剂量维生素D3对血管功能的影响。我们相信，这项研究也是第一次在分子水平上研究维生素D3补充对人类心脏代谢途径的关键介质的影响。如果我们的研究结果支持我们的工作假设，我们将提出一项更大规模的研究，以检测在更多样化的人群中对更明确、更临床的心血管终点的治疗效果。 假设：与安慰剂相比，维生素D缺乏会激活血管收缩和肥大介质，导致内皮功能障碍、血压升高和心血管疾病；与安慰剂相比，维生素D3重复补充(使用循证补充策略)将改善这些异常。