CLINICAL TRIAL: VITAMIN D PILOT (RTRN)

临床试验：维生素 D 试点 (RTRN)

基本信息

批准号：
8173593
负责人：
David Martins
金额：
$ 8.36万
依托单位：
CHARLES R. DREW UNIVERSITY OF MED & SCI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8173593
关键词：
Adult African American Blood Pressure Blood Vessels Cardiovascular Diseases Cardiovascular system Cause of Death Cholecalciferol Clinical Clinical Trials Computer Retrieval of Information on Scientific Projects Database Diabetes Mellitus Disease Dose Event Functional disorder Funding Grant Human Hypertension Institution Intervention Knowledge Lead Link Mediator of activation protein Metabolic Pathway Molecular Outcome Overweight Pathway interactions Placebo Control Placebos Population Population Heterogeneity Positioning Attribute Public Health Randomized Research Research Personnel Resources Source Subgroup Therapeutic Therapeutic Agents Therapeutic Effect Translating United States National Institutes of Health Vitamin D Vitamin Deficiency Vitamins Work cardiovascular risk factor ethnic minority population evidence base mortality pilot trial

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular Disease (CVD) and related disorders remain the leading cause of death in the nation1. Hypovitaminosis D has been linked not only to several cardiovascular (CV) risk factors including hypertension, diabetes, obesity2,3, but also to increased rates of CVD4,5,6. 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.7 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 doubleblind, 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.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。心血管疾病（CVD）和相关疾病仍然是该国死亡的主要原因1。维生素 D 缺乏不仅与高血压、糖尿病、肥胖等多种心血管 (CV) 危险因素相关2,3，而且还与 CVD 发病率增加相关4,5,6。因此，维生素 D 缺乏症是一个常见的为选定的亚组提供一条途径，该亚组的心血管危险因素在少数族裔中占主导地位。事实上，维生素 D 缺乏症非常普遍，估计 55% 的美国成年人维生素 D 水平等于或低于 30 ng/ml，超过 80% 的非裔美国人维生素 D 水平低于最佳水平。 7 大量证据支持这样一个前提：对血管功能具有有益作用的治疗药物通常会转化为对“更困难”的临床终点（例如不良心血管事件和死亡率）的治疗益处。探索补充维生素 D 对血管的潜在影响提供了一个独特的机会检查可能对公共卫生水平产生重大影响的潜在可修改干预措施的临床结果和具体机制途径。因此，我们提出了一项为期 12 周的随机双盲、安慰剂对照试点试验，以评估 100,000 IU 对血管功能和心血管危险因素的影响每 4 周向患有维生素 D 缺乏症的超重、高血压非裔美国人注射维生素 D3。据我们所知，该项目是第一个评估“高剂量”维生素 D3 给药对血管功能影响的项目。我们相信这项研究也是第一个在分子水平上检验补充维生素 D3 对人类心脏代谢途径关键介质的影响的研究。如果我们的研究结果支持我们的工作假设，我们将能够提出一项更大规模的研究，以检测对更多样化人群中更明确的临床心血管终点的治疗效果。假设：维生素 D 缺乏症会激活特定的血管收缩和肥大介质，导致内皮功能障碍、血压升高和 CVD；与安慰剂相比，补充维生素 D3（使用基于证据的补充策略）将改善这些异常。