Biomarkers to stratify pain severity and type in pancreatic disease

用于对胰腺疾病疼痛严重程度和类型进行分层的生物标志物

基本信息

  • 批准号:
    10707763
  • 负责人:
  • 金额:
    $ 77.81万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-15 至 2027-05-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Chronic pancreatitis (CP) results from progressive inflammation and fibrosis, most commonly from acute pancreatitis (AP) and recurrent episodes of AP (RAP), and is associated with long term complications of diabetes and exocrine pancreatic insufficiency. Pain is one of three diagnostic criteria for AP and multiple studies have now confirmed that pain is also the most significant symptom for patients with CP (77-93%). While there are a variety of interventions available to treat pain, many of which are not efficacious in CP patient: only ~25% chronic pancreatitis patients achieve meaningful pain relief with current standard of care for pain management. As of now, there are no chronic pancreatitis pain biomarkers to stratify pain based on severity and/or type, which would guide physician decision making or monitor therapeutic responses. This contributes to the immense burden of pain in this CP patient population. To address this gap in knowledge, we will leverage the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies (PROCEED) which has been realized under the auspice of the NIDDK-/ NCI-funded Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). PROCEED, which will be a key resource for this proposal, is the first prospective longitudinal CP cohort in the U.S. It has enrolled 1638 (and counting) participants with CP, AP, and RAP, as well as healthy and non- pancreatitis symptomatic controls. All participants of this unique cohort undergo deep phenotyping, provide detailed information on clinical symptoms, and general QoL variables. Furthermore, 10 pain-associated variables are recorded providing detailed information about pain types, severities and interventions. Due to the size and multi-site nature of PROCEED, the cohort was split into independent discovery and validation cohorts to enable FDA-compliant biomarker validation. In Specific Aims 1 and 2 of this proposal, we will use plasma and urine samples from the PROCEED discovery cohort (n >500) to generate quantitative multi-omics datasets of the proteins, chemokines, cytokines and neuropeptides. Mass spectrometry-based discovery proteomics and multiplexed antibody-based assays will be used for the biomarker identification. Upon discovery of promising pain biomarkers, we will transition to the validation phase (Specific Aims 3 and 4). In this phase, we will use the urine and plasma samples from the independent PROCEED validation cohort (n >500) to validate the potential biomarkers identified in the Specific Aims 1 and 2. We will use targeted liquid chromatography/mass spectrometry methods as well as antibody-based method for the validation. The large number of PROCEED samples and their superb annotation will allow for an exquisitely granular pain-focused analysis of the resulting large scale proteomic and cytokine/chemokine assay data.
项目摘要 慢性胰腺炎(CP)是由进行性炎症和纤维化引起的,最常见于急性 AP(RAP)的胰腺炎(AP)和复发发作,与糖尿病的长期并发症有关 和外分泌胰腺功能不全。疼痛是AP的三个诊断标准之一,多个研究具有 现在证实疼痛也是CP患者(77-93%)的最重要症状。那里 是否可以使用多种干预措施来治疗疼痛,其中许多在CP患者中不有效:只有约25% 慢性胰腺炎患者通过当前的疼痛护理标准来缓解有意义的疼痛 管理。截至目前,还没有慢性胰腺炎疼痛生物标志物来根据严重程度对疼痛进行分层 和/或类型,这将指导医师决策或监测治疗反应。这有助于 该CP患者人群的痛苦负担很大。 为了解决知识的这一差距,我们将利用对慢性胰腺炎的预期评估 流行病学和翻译研究(继续)已在Niddk-/ NCI资助的财团用于研究慢性胰腺炎,糖尿病和胰腺癌(CPDPC)。 继续是该提案的关键资源,是第一个前瞻性纵向CP队列 美国已招募了1638(且计数)参与者,并接受了CP,AP和RAP,以及健康且不 胰腺炎症状控制。这个独特队列的所有参与者都会进行深层表型,提供 有关临床症状和一般质量变量的详细信息。此外,10个疼痛相关变量 记录了有关疼痛类型,严重性和干预措施的详细信息。由于大小和 继续进行的多站点性质,该队列分为独立发现和验证队列以启用 符合FDA的生物标志物验证。在本提案的特定目的1和2中,我们将使用血浆和尿液 从“继续发现”同类(n> 500)中的样本生成定量的多摩变数据集 蛋白质,趋化因子,细胞因子和神经肽。基于质谱的发现蛋白质组学和 基于多抗体的测定将用于生物标志物识别。 发现有希望的疼痛生物标志物后,我们将过渡到验证阶段(特定目的3和4)。 在此阶段,我们将使用独立进行验证队列中的尿液和血浆样品(n > 500)验证特定目的1和2中确定的潜在生物标志物。我们将使用目标液体 色谱/质谱法以及基于抗体的验证方法。大 进行样本的数量及其出色的注释将允许精致的颗粒状疼痛 分析所得的大规模蛋白质组学和细胞因子/趋化因子测定数据。

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)

暂无数据

数据更新时间:2024-06-01

Jami Lynn Saloman的其他基金

Mechanism-based Approach to Pain in Chronic Pancreatitis (MAP-CP Study)
基于机制的慢性胰腺炎疼痛治疗方法(MAP-CP 研究)
  • 批准号:
    10263243
    10263243
  • 财政年份:
    2020
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Mechanism-based Approach to Pain in Chronic Pancreatitis (MAP-CP Study)
基于机制的慢性胰腺炎疼痛治疗方法(MAP-CP 研究)
  • 批准号:
    9976126
    9976126
  • 财政年份:
    2020
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Neuropathic vs. inflammatory pain in chronic pancreatitis: can unique biomarkers be identified to guide mechanistic approaches to pain treatment?
慢性胰腺炎的神经性疼痛与炎性疼痛:是否可以确定独特的生物标志物来指导疼痛治疗的机制方法?
  • 批准号:
    10335169
    10335169
  • 财政年份:
    2019
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Neuropathic vs. inflammatory pain in chronic pancreatitis: can unique biomarkers be identified to guide mechanistic approaches to pain treatment?
慢性胰腺炎的神经性疼痛与炎性疼痛:是否可以确定独特的生物标志物来指导疼痛治疗的机制方法?
  • 批准号:
    9902440
    9902440
  • 财政年份:
    2019
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Neuropathic vs. inflammatory pain in chronic pancreatitis: can unique biomarkers be identified to guide mechanistic approaches to pain treatment?
慢性胰腺炎的神经性疼痛与炎性疼痛:是否可以确定独特的生物标志物来指导疼痛治疗的机制方法?
  • 批准号:
    10555264
    10555264
  • 财政年份:
    2019
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Neuropathic vs. inflammatory pain in chronic pancreatitis: can unique biomarkers be identified to guide mechanistic approaches to pain treatment?
慢性胰腺炎的神经性疼痛与炎性疼痛:是否可以确定独特的生物标志物来指导疼痛治疗的机制方法?
  • 批准号:
    10083736
    10083736
  • 财政年份:
    2019
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Functional Interactions Between Peripheral P2X3 and TRP Channels
外设 P2X3 和 TRP 通道之间的功能交互
  • 批准号:
    8261843
    8261843
  • 财政年份:
    2011
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Functional Interactions Between Peripheral P2X3 and TRP Channels
外设 P2X3 和 TRP 通道之间的功能交互
  • 批准号:
    8060323
    8060323
  • 财政年份:
    2011
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:

相似国自然基金

抗翻译后修饰清道夫受体SR-A多肽抗体在类风湿关节炎中的诊断价值、致病作用及免疫机制研究
  • 批准号:
    82371807
  • 批准年份:
    2023
  • 资助金额:
    49 万元
  • 项目类别:
    面上项目
FcγRI介导系统性红斑狼疮自身抗体IgG诱导的非侵蚀性关节炎机制的研究
  • 批准号:
    82171786
  • 批准年份:
    2021
  • 资助金额:
    54.00 万元
  • 项目类别:
    面上项目
FcγRI介导系统性红斑狼疮自身抗体IgG诱导的非侵蚀性关节炎机制的研究
  • 批准号:
  • 批准年份:
    2021
  • 资助金额:
    54 万元
  • 项目类别:
    面上项目
抗半乳糖醛酸聚糖(PGA)抗体在诱导类风湿关节炎骨侵蚀中的作用
  • 批准号:
    81972041
  • 批准年份:
    2019
  • 资助金额:
    55 万元
  • 项目类别:
    面上项目
滤泡调节性T细胞(TFR)在类风湿性关节炎发生和发展中的作用及其相关机制研究
  • 批准号:
    81871230
  • 批准年份:
    2018
  • 资助金额:
    57.0 万元
  • 项目类别:
    面上项目

相似海外基金

Developing Tools to Understand an Alternative Fate of Urate in Neurodegenerative Diseases
开发工具来了解尿酸盐在神经退行性疾病中的替代命运
  • 批准号:
    10668103
    10668103
  • 财政年份:
    2023
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
A Potent D-peptide Inhibitor of TNFα for Treatment of Rheumatoid Arthritis
一种有效的 TNFα D 肽抑制剂,用于治疗类风湿性关节炎
  • 批准号:
    10822182
    10822182
  • 财政年份:
    2023
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Validation of the joint-homing and drug delivery attributes of novel peptides in a mouse arthritis model
在小鼠关节炎模型中验证新型肽的关节归巢和药物递送特性
  • 批准号:
    10589192
    10589192
  • 财政年份:
    2023
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
Role of antiviral signaling in psoriatic pathogenesis
抗病毒信号在银屑病发病机制中的作用
  • 批准号:
    10643178
    10643178
  • 财政年份:
    2023
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别:
A simulation platform to predict dose and therapeutic window of immunocytokines
预测免疫细胞因子剂量和治疗窗的模拟平台
  • 批准号:
    10698708
    10698708
  • 财政年份:
    2023
  • 资助金额:
    $ 77.81万
    $ 77.81万
  • 项目类别: