URGE

敦促

基本信息

  • 批准号:
    8340712
  • 负责人:
  • 金额:
    $ 2.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-08-01 至 2013-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Urge urinary incontinence (UUI), characterized by unpredictable and embarrassing large volume urine leakage, is a major public health burden to elderly women given its high prevalence, impairment of quality of life, associated caregiver burden and substantial economic costs. Anticholinergic medications are the most common first-line therapy for urge incontinence. While anticholinergics are efficacious, their effectiveness is limited by poor response or adverse events (AEs) in certain individuals. Unfortunately, we are unable to predict an individual patient's response to anticholinergics, leading to empiric pharmacotherapy. A novel approach to personalize drug therapy is pharmacogenetics. Specifically, fesoterodine is metabolized by a well characterized cytochrome P450 (CYP) enzyme, CYP2D6. The CYP2D6 gene has several genetic variants, which result in different metabolizer statuses. These CYP2D6 profiles may be clinically important because of the greater likelihood of low efficacy in fast metabolizers due to low plasma drug concentrations, and the higher risk of AEs among slow metabolizers due to high drug concentrations. The ability to use CYP2D6 metabolizer status to predict which subjects will experience low efficacy or develop moderate to severe adverse events to fesoterodine would challenge existing therapeutic approaches and would significantly advance clinical practice. Hence, our specific aims are: 1) To evaluate whether CYP2D6 metabolizer status is correlated with efficacy during 4 weeks of fesoterodine therapy in elderly women with UUI; 2) To assess whether CYP2D6 metabolizer status is correlated with moderate to severe adverse events during 4 weeks of fesoterodine therapy, and 3) To utilize preliminary data collected from this proof-of-concept, pilot study to plan a large-scale trial to predict outcomes of anticholinergic therapy based on CYP2D6 metabolizer status. This innovative proposal represents a meaningful shift into aging research for the PI, Dr. Jennifer Wu, and would launch her career into aging science and would establish this multidisciplinary, collaborative team of urogynecologists, geriatricians, pharmacogeneticists and statistical geneticists. Furthermore, this pioneering pharmacogenetic research has the potential to lay essential groundwork for future long-term research which would optimize and personalize UUI therapy for millions of elderly women. PUBLIC HEALTH RELEVANCE: Urge urinary incontinence, characterized by unpredictable and embarrassing large volume urine leakage, is a major health issue for elderly women, as it is incredibly common and significantly impairs quality of life. Although anticholinergic medications are the most common therapy, we are unable to predict an individual's response to a particular drug in terms of both effectiveness and side effects. Through genetic evaluation, we have the potential to personalize and optimize drug therapy for millions of elderly women suffering from urge incontinence.
描述(由申请人提供):急迫性尿失禁(UUI)的特点是不可预测且令人尴尬的大量尿液漏出,由于其患病率高、生活质量受损、相关的护理负担和巨大的经济成本,它是老年妇女的主要公共卫生负担。抗胆碱能药物是急迫性尿失禁最常见的一线治疗方法。虽然抗胆碱能药物有效,但其有效性受到某些个体反应不佳或不良事件 (AE) 的限制。不幸的是,我们无法预测个体患者对抗胆碱能药物的反应,从而导致经验性药物治疗。个体化药物治疗的一种新方法是药物遗传学。具体来说,非索罗定由一种已充分表征的细胞色素 P450 (CYP) 酶 CYP2D6 代谢。 CYP2D6 基因有多种遗传变异,导致不同的代谢状态。这些 CYP2D6 谱可能具有临床重要意义,因为血浆药物浓度低导致快代谢者更有可能出现低疗效,而慢代谢者由于药物浓度高而发生 AE 的风险更高。使用 CYP2D6 代谢状态来预测哪些受试者将经历低效或发生中度至重度非索罗定不良事件的能力将挑战现有的治疗方法,并将显着推进临床实践。因此,我们的具体目标是: 1) 评估 CYP2D6 代谢状态是否与患有 UUI 的老年女性接受非索罗定治疗 4 周期间的疗效相关; 2) 评估 CYP2D6 代谢状态是否与 4 周非索罗定治疗期间的中度至重度不良事件相关,以及 3) 利用从该概念验证试点研究中收集的初步数据来计划一项大规模试验,以根据 CYP2D6 代谢状态预测抗胆碱能治疗的结果。这项创新提案代表了 PI Jennifer Wu 博士在衰老研究领域的一次有意义的转变,并将开启她在衰老科学领域的职业生涯,并建立这个由泌尿妇科医生、老年病学家、药物遗传学家和统计遗传学家组成的多学科协作团队。此外,这项开创性的药物遗传学研究有可能为未来的长期研究奠定必要的基础,从而优化和个性化数百万老年妇女的 UUI 治疗。 公共卫生相关性:急迫性尿失禁的特点是不可预测且令人尴尬的大量尿液漏出,是老年妇女的一个主要健康问题,因为它非常常见,并且严重损害生活质量。尽管抗胆碱能药物是最常见的治疗方法,但我们无法预测个体对特定药物的有效性和副作用的反应。通过基因评估,我们有可能为数百万患有急迫性尿失禁的老年妇女提供个性化和优化的药物治疗。

项目成果

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JENNIFER M. WU其他文献

JENNIFER M. WU的其他文献

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{{ truncateString('JENNIFER M. WU', 18)}}的其他基金

URGE
敦促
  • 批准号:
    8516949
  • 财政年份:
    2012
  • 资助金额:
    $ 2.69万
  • 项目类别:
URGE
敦促
  • 批准号:
    8650376
  • 财政年份:
    2012
  • 资助金额:
    $ 2.69万
  • 项目类别:
Translational Research in Pelvic Floor Disorders
盆底疾病的转化研究
  • 批准号:
    8703627
  • 财政年份:
    2011
  • 资助金额:
    $ 2.69万
  • 项目类别:
Translational Research in Pelvic Floor Disorders
盆底疾病的转化研究
  • 批准号:
    8466246
  • 财政年份:
    2011
  • 资助金额:
    $ 2.69万
  • 项目类别:
Translational Research in Pelvic Floor Disorders
盆底疾病的转化研究
  • 批准号:
    8091090
  • 财政年份:
    2011
  • 资助金额:
    $ 2.69万
  • 项目类别:
Translational Research in Pelvic Floor Disorders
盆底疾病的转化研究
  • 批准号:
    8261921
  • 财政年份:
    2011
  • 资助金额:
    $ 2.69万
  • 项目类别:
Genetic Epidemiology of Pelvic Organ Prolapse
盆腔器官脱垂的遗传流行病学
  • 批准号:
    7893258
  • 财政年份:
    2009
  • 资助金额:
    $ 2.69万
  • 项目类别:
Genetic Epidemiology of Pelvic Organ Prolapse
盆腔器官脱垂的遗传流行病学
  • 批准号:
    7724796
  • 财政年份:
    2009
  • 资助金额:
    $ 2.69万
  • 项目类别:

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