Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Tradipitant for Functional Dyspepsia

Tradpitant 治疗功能性消化不良的药效学、药物遗传学、临床疗效和安全性

基本信息

  • 批准号:
    10409418
  • 负责人:
  • 金额:
    $ 31.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-04-20 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

ABSTRACT 30 lines (currently 30) Upper gastrointestinal symptoms may result from gastric dysfunction including reduced gastric accommodation and gastric hypersensitivity, and may cause functional dyspepsia (FD), a very common cause of substantial morbidity estimated to affect 10% of the population. FD manifests as abdominal pain/discomfort for at least three days per week which may be associated with eating. An estimated 40% of patients with this symptom complex consult their physicians, negatively influencing their workplace attendance and productivity with overall economic impact of more than $18 billion in 2009. Development of effective treatments of these disorders is desirable, given significant unmet medical need. Systematic reviews and meta-analyses of the literature have shown low levels of efficacy with current treatments which include proton pump inhibitors, H pylori eradication, prokinetics, and central neuromodulators. There is currently no approved treatment for functional dyspepsia. We have developed a noninvasive imaging method to simultaneously measure gastric accommodation and gastric emptying, one or both of which are reported to be altered in up to 75% of patients with functional dyspepsia. The approved NK 1 receptor (NK1R) antagonist aprepitant has been shown to increase fasting gastric volume and postprandial accommodation in healthy participants without deleteriously affecting gastric emptying. The novel NK1R antagonist, tradipitant, was previously shown to reduce symptoms in patients with gastroparesis although the precise mechanism, overall effects, and benefit-risk ratio of this medication unclear. Our general hypothesis is that tradipitant relieves symptoms in patients with functional dyspepsia as well as enhances postprandial gastric accommodation without deleterious effects on gastric emptying. Our aims are: 1. To compare the pharmacodynamics and clinical effects of tradipitant vs. placebo on satiation, fasting and fed gastric volume, gastric accommodation, gastric emptying, and symptoms in patients with functional dyspepsia (and non-delayed gastric emptying at baseline) based on Leuven Dyspepsia scale and Nepean Dyspepsia Index 2. To assess prevalence of NKR-SNP rs881 genetic variant and the pharmacogenetics effects of this variant in NK1 gene on the pharmacodynamics of tradipitant compared to placebo on fasting and accommodation gastric volumes, gastric emptying and satiation. In an exploratory analysis, we shall assess the correlation between gastric accommodation and emptying in functional dyspepsia and to compare the relationship with those previously reported in health volunteers. Anticipated Results and Significance: We expect these studies will lead to understanding the mechanisms of action of tradipitant in improving gastrointestinal functions and patient reported outcomes, including pain, in patients with functional dyspepsia, addressing unmet needs of millions of American citizens.
抽象的 30行(目前30行) 胃肠道症状上限可能是胃功能障碍引起的 和胃超敏反应,并可能引起功能性消化不良(FD),这是实质性的非常普遍的原因 发病率估计会影响10%的人口。 FD至少表现为腹部疼痛/不适 每周三天可能与饮食有关。估计有40%的患有此症状的患者 复杂的咨询医生,对他们的工作场所的出勤率和生产力产生负面影响 2009年超过180亿美元的总体经济影响。 鉴于巨大的未满足医疗需求,疾病是可取的。系统评价和荟萃分析 文献表明,通过包括质子泵抑制剂在内的当前治疗方法的疗效水平较低 幽门螺杆菌根除,原核生物和中央神经调节剂。目前尚无批准的治疗 功能障碍。我们已经开发了一种无创成像方法来同时测量胃 住宿和胃排空,据报道,其中一种或两者在多达75%的患者中被改变 功能性消化不良。已证明已批准的NK 1受体(NK1R)拮抗剂载体已显示为 在没有有害的健康参与者中增加禁食胃量和餐后住宿 影响胃排空。以前显示出新型的NK1R拮抗剂Travipitant可以减轻症状 在胃轻瘫的患者中,尽管精确的机制,总体效果和利益风险比率 药物不清楚。我们的总体假设是,tra脚可缓解功能性患者的症状 消化不良并增强餐后胃套住宿,对胃而没有有害影响 排空。我们的目标是: 1。比较tra脚的药效学和临床作用与安慰剂对饱食,禁食和 功能性患者的胃量,胃排空,胃排空和症状 基于leuven debspepsia量表和Nepean 消化不良指数 2。评估NKR-SNP RS881遗传变异的患病率和该变体的药物遗传学作用 与安慰剂相比,禁食和住宿胃的安慰剂相比 量,胃排空和饱腹感。 在探索性分析中,我们将评估胃住宿与排空之间的相关性 功能性消化不良并将这种关系与先前在卫生志愿者中报道的关系进行比较。 预期的结果和意义:我们希望这些研究将导致理解机制 在改善胃肠道功能和患者报告的结果(包括疼痛)中 功能性消化不良的患者满足了数百万美国公民的未满足需求。

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 }}

Xiao Jing Wang其他文献

Xiao Jing Wang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('Xiao Jing Wang', 18)}}的其他基金

Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Tradipitant for Functional Dyspepsia
Tradpitant 治疗功能性消化不良的药效学、药物遗传学、临床疗效和安全性
  • 批准号:
    10611491
  • 财政年份:
    2022
  • 资助金额:
    $ 31.55万
  • 项目类别:

相似国自然基金

肠易激综合征(IBS)腹痛的细胞和分子机制研究
  • 批准号:
    81971046
  • 批准年份:
    2019
  • 资助金额:
    55 万元
  • 项目类别:
    面上项目
中枢介导的腹痛综合征患者大脑多模态磁共振成像研究
  • 批准号:
    81800482
  • 批准年份:
    2018
  • 资助金额:
    21.0 万元
  • 项目类别:
    青年科学基金项目
疏肝健脾法通过调控组蛋白乙酰化修饰降低肝郁脾虚IBS-D内脏高敏感的机制研究
  • 批准号:
    81703955
  • 批准年份:
    2017
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目
基于PKCγ/ERK1/2/MAPK信号通路探讨安肠汤缓解腹泻型肠易激综合征腹痛研究
  • 批准号:
    81560754
  • 批准年份:
    2015
  • 资助金额:
    39.0 万元
  • 项目类别:
    地区科学基金项目
针刺治疗功能性消化不良上腹痛综合征的疼痛记忆淡化机制研究
  • 批准号:
    81473602
  • 批准年份:
    2014
  • 资助金额:
    73.0 万元
  • 项目类别:
    面上项目

相似海外基金

Pharmacodynamics, Pharmacogenetics, Clinical Efficacy and Safety of Tradipitant for Functional Dyspepsia
Tradpitant 治疗功能性消化不良的药效学、药物遗传学、临床疗效和安全性
  • 批准号:
    10611491
  • 财政年份:
    2022
  • 资助金额:
    $ 31.55万
  • 项目类别:
Fecal microbiota, short chain fatty acids, bile acids, and colonic transit in Irritable Bowel Syndrome
肠易激综合症中的粪便微生物群、短链脂肪酸、胆汁酸和结肠运输
  • 批准号:
    10671301
  • 财政年份:
    2019
  • 资助金额:
    $ 31.55万
  • 项目类别:
Fecal microbiota, short chain fatty acids, bile acids, and colonic transit in Irritable Bowel Syndrome
肠易激综合症中的粪便微生物群、短链脂肪酸、胆汁酸和结肠运输
  • 批准号:
    10158484
  • 财政年份:
    2019
  • 资助金额:
    $ 31.55万
  • 项目类别:
Fecal microbiota, short chain fatty acids, bile acids, and colonic transit in Irritable Bowel Syndrome
肠易激综合症中的粪便微生物群、短链脂肪酸、胆汁酸和结肠运输
  • 批准号:
    9805532
  • 财政年份:
    2019
  • 资助金额:
    $ 31.55万
  • 项目类别:
Fecal microbiota, short chain fatty acids, bile acids, and colonic transit in Irritable Bowel Syndrome
肠易激综合症中的粪便微生物群、短链脂肪酸、胆汁酸和结肠运输
  • 批准号:
    10408145
  • 财政年份:
    2019
  • 资助金额:
    $ 31.55万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了