Precision Medicine Approach to Vitamin D3 Administration in Critical Illness

危重疾病维生素 D3 给药的精准医学方法

基本信息

  • 批准号:
    10444999
  • 负责人:
  • 金额:
    $ 44.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-01 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Acute respiratory distress syndrome (ARDS) is a common and devastating complication of critical illness, and effective therapies to prevent ARDS are limited. Vitamin D metabolites have potent immunomodulatory effects and attenuate acute organ injury in animal models. Randomized controlled trials (RCTs) are ongoing to test whether vitamin D3 (vit D3) administration improves outcomes in critically ill patients at risk of ARDS. However, due to the heterogeneous nature of critical illness, patient-specific factors likely play a major role in determining response to vit D3. We will use a precision medicine approach to investigate the clinical, genetic, and biochemical factors that determine response to vit D3 administration in critical illness. This proposal is an ancillary study to the NHLBI-funded Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET) trial, an ongoing, multicenter RCT that is enrolling 3000 critically ill patients at high risk of ARDS and death. Patients are randomly assigned to receive a single enteral dose of 540,000 I.U. of vit D3 or placebo to test whether vit D3 reduces 90-day mortality and acute organ injury. VIOLET is archiving plasma and DNA from all 3000 patients on day 0, and plasma on day 3 from the first 300 patients. We propose to collect plasma on day 3 from an additional 500 patients (Aim 1) and to leverage existing samples (Aims 2 and 3) to test the following hypotheses. In Aim 1 we will use paired plasma samples (n=400) from days 0 and 3 to investigate the clinical factors that affect the pharmacokinetic response to vit D3 administration in critical illness. We will test whether greater severity-of-illness (higher SOFA score), obesity, and acute or chronic liver or kidney disease attenuate increases in plasma 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) levels from day 0 to 3 in patients who receive vit D3. In Aim 2 we will investigate whether pre-specified common polymorphisms in genes affecting vitamin D metabolism or in vitamin D target genes identify a patient population more likely to benefit from vit D3 administration, assessed by 90-day mortality (primary endpoint) and acute organ injury (secondary endpoint). In Aim 3, we will investigate whether lower plasma levels of fibroblast growth factor-23, an osteocyte-derived hormone that inhibits the conversion of 25D to 1,25D, identify a patient population more likely to benefit from vit D3 administration, assessed by 90-day mortality (primary endpoint) and acute organ injury (secondary endpoint). Development of a precision medicine approach to vit D3 administration in critical illness could have immediate and actionable clinical impact by helping to inform both clinical decision making and the design of future trials of vitamin D metabolites in critical illness.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

David Evan Leaf其他文献

David Evan Leaf的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('David Evan Leaf', 18)}}的其他基金

Hepcidin-Ferroportin-Iron Axis in Cardiac Surgery-associated Acute Kidney Injury
心脏手术相关急性肾损伤中的铁调素-铁转运蛋白-铁轴
  • 批准号:
    10659183
  • 财政年份:
    2022
  • 资助金额:
    $ 44.34万
  • 项目类别:
Hepcidin-Ferroportin-Iron Axis in Cardiac Surgery-associated Acute Kidney Injury
心脏手术相关急性肾损伤中的铁调素-铁转运蛋白-铁轴
  • 批准号:
    10444522
  • 财政年份:
    2022
  • 资助金额:
    $ 44.34万
  • 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
  • 批准号:
    10670112
  • 财政年份:
    2020
  • 资助金额:
    $ 44.34万
  • 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
  • 批准号:
    10442625
  • 财政年份:
    2020
  • 资助金额:
    $ 44.34万
  • 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
  • 批准号:
    10249293
  • 财政年份:
    2020
  • 资助金额:
    $ 44.34万
  • 项目类别:
Deferoxamine for the Prevention of Acute Kidney Injury
去铁胺预防急性肾损伤
  • 批准号:
    10034169
  • 财政年份:
    2020
  • 资助金额:
    $ 44.34万
  • 项目类别:
Precision Medicine Approach to Vitamin D3 Administration in Critical Illness
危重疾病维生素 D3 给药的精准医学方法
  • 批准号:
    9916797
  • 财政年份:
    2019
  • 资助金额:
    $ 44.34万
  • 项目类别:
Precision Medicine Approach to Vitamin D3 Administration in Critical Illness
危重疾病维生素 D3 给药的精准医学方法
  • 批准号:
    10217234
  • 财政年份:
    2019
  • 资助金额:
    $ 44.34万
  • 项目类别:
Dysregulated Mineral Metabolism in Acute Kidney Injury
急性肾损伤时矿物质代谢失调
  • 批准号:
    8702918
  • 财政年份:
    2013
  • 资助金额:
    $ 44.34万
  • 项目类别:
Dysregulated Mineral Metabolism in Acute Kidney Injury
急性肾损伤时矿物质代谢失调
  • 批准号:
    8588596
  • 财政年份:
    2013
  • 资助金额:
    $ 44.34万
  • 项目类别:

相似海外基金

Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
  • 批准号:
    MR/Y009568/1
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
  • 批准号:
    10090332
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
  • 批准号:
    MR/X02329X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
  • 批准号:
    MR/X021882/1
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
  • 批准号:
    MR/X029557/1
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
  • 批准号:
    EP/Y003527/1
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
  • 批准号:
    EP/Y030338/1
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
  • 批准号:
    2312694
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
  • 批准号:
    24K19395
  • 财政年份:
    2024
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
  • 批准号:
    484000
  • 财政年份:
    2023
  • 资助金额:
    $ 44.34万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了