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: 10474553
• 负责人: Evan L Fogel
• 金额: $ 44.97万
• 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/10474553
• 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; 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