Indiana University (IU) Clinical Center for Chronic Pancreatitis Clinical Research Network

印第安纳大学 (IU) 慢性胰腺炎临床中心临床研究网络

• 批准号: 10252055
• 负责人: Evan L Fogel
• 金额: $ 46.1万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10252055
• 关键词: Abdominal Pain; Acute; Address; Adult; Ancillary Study; Antiepileptic Agents; Bicarbonates; Biological; Biological Markers; Characteristics; Child; Childhood; Clinical; Clinical Research; Clinical Treatment; Data; Development; Diabetes Mellitus; Diagnosis; Disease; Disease Progression; Dose; Dose-Limiting; Duct (organ) structure; Duodenum; Early Diagnosis; Endocrine; Enrollment; Epidemiology; Excision; Exocrine pancreas; Extracorporeal Shockwave Lithotripsy; Fibrosis; Functional disorder; Funding; Galectin 3; Glucose Metabolism Disorders; Goals; Health Care Costs; Hormonal; Human; Hyperalgesia; Indiana; Individual; Institutes; Intervention; Investigation; Lead; Liquid substance; Lithotripsy; Liver Fibrosis; Longitudinal Studies; Magnetic Resonance Cholangiopancreatography; Magnetic Resonance Imaging; Main pancreatic duct; Malignant neoplasm of pancreas; Non-Insulin-Dependent Diabetes Mellitus; Onset of illness; Operative Surgical Procedures; Opioid; Organ; Pain; Pain management; Pancreas; Pancreatic Duct Stone; Patient Care; Patients; Phase; Placebos; Population; Procedures; Progressive Disease; Quality of life; Randomized; Randomized Controlled Trials; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Safety; Secondary to; Sensory; Serum; Site; Suggestion; System; Testing; Tissues; Toxic effect; United States National Institutes of Health; Universities; biomarker development; biomedical referral center; blood glucose regulation; candidate marker; carbohydrate binding protein; chronic pain; chronic pancreatitis; clinical center; clinical practice; cohort; comparative efficacy; cost; dermatome; early onset; effective therapy; experience; fibrogenesis; genetic variant; health care service utilization; high risk; improved; individual patient; inhibitor/antagonist; innovation; insight; nonalcoholic steatohepatitis; novel; opioid therapy; opioid use; pain relief; pain score; pancreatic juice; patient subsets; phase 1 study; pilot trial; predict clinical outcome; predictive test; pressure; primary endpoint; primary outcome; profiles in patients; randomized trial; response; secondary outcome; success; tool; treatment response

PROJECT SUMMARY / ABSTRACT Chronic pancreatitis (CP) is a progressive disease, often leading to loss of exocrine and endocrine function and debilitating abdominal pain. It is unknown why some individuals progress and develop complications, including pancreatogenic diabetes (T3cDM) and/or pancreas cancer (PDAC). In this Consortium, investigators have proposed and initiated several well-powered studies of risk factors, environmental influences, and proof-of-concept studies to move the field forward, particularly those factors that increase the risk of T3cDM and PDAC. Many of these studies are ongoing, while new innovative proposals will address other research objectives identified by the participating NIH institutes. We propose several specific aims (SA) to meet the goals of RFA-DK-19-009. In SA #1, we propose to continue the CPDPC's three main longitudinal studies: PROCEED, INSPPIRE 2 and NOD, as well as those two studies designed to better define and characterize T3cDM, DETECT and DEPICT. In SA #2, we propose to continue the ancillary study begun during the first funding cycle, specifically MINIMAP. SA #3: Galectin-3 (Gal-3) is a carbohydrate-binding protein which appears to be involved in fibrogenesis and tissue remodeling in CP. A Gal-3 inhibitor is safe and shows potential for reducing hepatic fibrosis in non-alcoholic steatohepatitis. We propose to test the hypothesis that a Gal-3 inhibitor is safe and efficacious in patients with CP, and may reverse or halt the fibrosis observed in CP. We will evaluate changes in pancreatic fibrosis as assessed by MRI, as well as serum and pancreatic fluid exploratory biomarkers. In SA #4, we propose innovative studies evaluating different strategies and interventions focused on alleviating abdominal pain in CP patients. Lacosamide, an anti-epileptic drug, appears to inhibit opioid-induced hyperalgesia. In SA #4a, we will perform a dose-escalation trial to evaluate the safety and tolerability of adding lacosamide to opioid therapy, followed by a pilot randomized trial to obtain preliminary data regarding change in pain control, opioid use and quality of life after adding lacosamide to an opioid. SA #4b: Quantitative sensory testing (QST) uses electrical and pressure stimulation at different dermatomes in order to unravel the pain system. We will investigate: (i) the association between QST profiles and demographic and clinical characteristics in patients with suspected or definite CP; (ii) whether the QST profile can be used to predict the clinical outcome of endoscopic or surgical treatment. SA #4c: Pancreatic duct stones may complicate CP, contributing to abdominal pain, and removal of these stones at ERCP frequently leads to significant pain relief. In this proposal, we compare the efficacy of two adjunctive procedures to ERCP for the treatment of main pancreatic duct stones in painful CP.

项目摘要 /摘要 慢性胰腺炎（CP）是一种进行性疾病，通常导致外分泌和内分泌丧失 功能和使腹痛使人衰弱。未知为什么有些人进步和 发展并发症，包括胰腺生成糖尿病（T3CDM）和/或胰腺癌 （PDAC）。在这个财团中，调查人员提出并发起了几个驱动力 研究风险因素，环境影响和概念验证研究以移动现场 向前，尤其是那些增加T3CDM和PDAC风险的因素。其中许多 研究正在进行中，而新的创新建议将解决其他研究目标 由参与的NIH机构确定。我们提出了几个特定目标（SA）来满足 RFA-DK-19-009的目标。在SA＃1中，我们建议继续CPDPC的三个主要纵向 研究：继续，Insppire 2和点头，以及旨在更好地定义的两项研究 并描述T3CDM，检测和描绘。在SA＃2中，我们建议继续辅助 研究在第一个融资周期开始，特别是最小值。 SA＃3：Galectin-3（Gal-3）是一个 碳水化合物结合蛋白似乎参与纤维发生和组织重塑 在CP中。 GAL-3抑制剂是安全的，并且显示出降低非酒精性肝纤维化的潜力 脂肪性肝炎。我们建议检验以下假设：GAL-3抑制剂在 CP患者，可能会逆转或停止在CP中观察到的纤维化。我们将评估更改 在MRI评估的胰腺纤维化以及血清和胰液探索性中 生物标志物。在SA＃4中，我们提出了评估不同策略和的创新研究 干预措施的重点是减轻CP患者的腹痛。 lacosamide，一种抗癫痫病 药物似乎抑制阿片类药物诱导的痛觉过敏。在SA＃4A中，我们将执行剂量升级 试验以评估将lacosamide添加到阿片类药物疗法的安全性和耐受性，然后是 试验随机试验以获取有关疼痛控制，阿片类药物使用和的初步数据 在阿片类药物中添加lacosamide后的生活质量。 SA＃4B：定量感觉测试（QST） 在不同的皮肤上使用电和压力刺激以弄清疼痛 系统。我们将调查：（i）QST配置文件与人口统计以及 怀疑或确定CP患者的临床特征； （ii）QST配置文件是否可以 用于预测内窥镜或手术治疗的临床结果。 SA＃4C：胰腺 管道可能使CP复杂化，导致腹痛，并在 ERCP经常导致明显的疼痛缓解。在此提案中，我们比较了两个 ERCP的辅助程序，用于治疗疼痛CP中主要胰管结石。