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: 10888561
• 负责人: Evan L Fogel
• 金额: $ 21.4万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-03 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10888561
• 关键词: Abdominal Pain; Acute; Adult; Appearance; Arginine; Beta Cell; Bicarbonates; Biological; Biological Markers; Cell physiology; Child; Childhood; Clinical; Clinical Research; Closure by clamp; Diabetes Mellitus; Diagnosis; Diagnostic; Diffusion; Disease; Disease Management; Disease Progression; Duodenum; Endocrine; Enrollment; Epidemiology; Evaluation; Exocrine pancreas; Fibrosis; Functional disorder; Funding; Galectin 3; Goals; Health Care Costs; Hormonal; Human; Hyperglycemia; Indiana; Individual; Inflammation; Institution; Liquid substance; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Metabolic; Natural History; Non-Insulin-Dependent Diabetes Mellitus; OGTT; Onset of illness; Organ; Pancreas; Pancreatic Diseases; Pathogenesis; Patients; Pharmaceutical Preparations; Phenotype; Physiological; Population; Population Control; Prevalence; Progressive Disease; Prospective Studies; Quality of life; Research Personnel; Resources; Risk; Risk Factors; Safety; Secondary to; Secretin; Signal Transduction; Specimen; Testing; Tissues; Universities; Work; biomedical referral center; blood glucose regulation; candidate marker; carbohydrate binding protein; carbohydrate receptor; chronic pain; chronic pancreatitis; clinical center; diabetes risk; disease diagnosis; early onset; experience; fibrogenesis; genetic variant; improved; inhibitor; insight; islet; member; observational cohort study; pain score; profiles in patients; prospective; randomized placebo controlled trial; 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 (PDM) and/or pancreas cancer (PDAC). In this consortium, investigators propose to conduct 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 PDM and PDAC. We propose the following specific aims (SA) to meet the goals of RFA-DK-14-027. SA #1: To define the natural history of pediatric and adult patients with an established diagnosis of CP or acute recurrent pancreatitis, we propose a prospective observational cohort study. We will place emphasis on identifying risk factors and phenotypes for those patients who develop PDM and/or PDAC. Biological specimens will be obtained to facilitate the study of possible biomarkers which might facilitate early disease diagnosis and management. SA #2: The pathogenesis of PDM and the interactions of non-endocrine pancreatic disease with islet dysfunction are not well understood. We will use measurements of islet function (oral glucose tolerance tests, arginine- augmented hyperglycemic clamps) in cross-sectional and prospective studies to define the prevalence and physiologic basis for metabolic dysregulation and diabetes in CP. We will also prospectively ascertain changes in islet function and transition to overt PDM, and correlate changes in metabolic status with changes in pancreatic inflammation and function. SA #3: To evaluate the diagnostic efficacy of Magnetic Resonance (MR) imaging in the non-invasive evaluation of suspected early CP, we propose a prospective study comparing CP patients to a control population with normal pancreatic exocrine function. A reduced T1-weighted MR signal, reduced diffusion and decreased duodenal fluid volume in response to secretin stimulation may suggest CP. SA #4: 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 appears to be safe and shows potential for reducing organ fibrosis in humans. To determine the safety and efficacy of a Gal-3 inhibitor, we propose a randomized placebo- controlled trial in 66 CP patients. Improvement in post-therapy duodenal fluid bicarbonate level will be the primary efficacy endpoint. We anticipate that this drug will reverse fibrosis, as manifested by improvement in duodenal bicarbonate level. Additional endpoints including MRI/MRCP appearance, Gal-3 level, quality of life, abdominal pain scores and β-cell function will also be assessed.

项目摘要/摘要

项目成果

Detection of exocrine dysfunction by MRI in patients with early chronic pancreatitis.

• DOI: 10.1007/s00261-016-0917-2
• 发表时间: 2017-03
• 期刊: Abdominal radiology (New York)
• 作者: Tirkes T;Fogel EL;Sherman S;Lin C;Swensson J;Akisik F;Sandrasegaran K
• 通讯作者: Sandrasegaran K

Secretin-Enhanced MRCP: How and Why-AJR Expert Panel Narrative Review.

Secralin增强的MRCP：如何以及为什么AJR专家小组叙事评论。

• DOI: 10.2214/ajr.20.24857
• 发表时间: 2021-05
• 期刊: AJR. American journal of roentgenology
• 作者: Swensson J;Zaheer A;Conwell D;Sandrasegaran K;Manfredi R;Tirkes T
• 通讯作者: Tirkes T

Quantitative MR Evaluation of Chronic Pancreatitis: Extracellular Volume Fraction and MR Relaxometry.

• DOI: 10.2214/ajr.17.18606
• 发表时间: 2018-03
• 期刊: AJR. American journal of roentgenology
• 作者: Tirkes T;Lin C;Cui E;Deng Y;Territo PR;Sandrasegaran K;Akisik F
• 通讯作者: Akisik F

Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.

• DOI: 10.1016/s2468-1253(19)30337-1
• 发表时间: 2020-02
• 期刊: LANCET GASTROENTEROLOGY & HEPATOLOGY
• 影响因子: 35.7
• 作者: Fogel, Evan L.;Lehman, Glen A.;Tarnasky, Paul;Cote, Gregory A.;Schmidt, Suzette E.;Waljee, Akbar K.;Higgins, Peter D. R.;Watkins, James L.;Sherman, Stuart;Kwon, Richard S. Y.;Elta, Grace H.;Easler, Jeffrey J.;Pleskow, Douglas K.;Scheiman, James M.;El Hajj, Ihab I.;Guda, Nalini M.;Gromski, Mark A.;McHenry, Lee, Jr.;Arol, Seena;Korsnes, Sheryl;Suarez, Alejandro L.;Spitzer, Rebecca;Miller, Marilyn;Hofbauer, Maria;Elmunzer, B. Joseph
• 通讯作者: Elmunzer, B. Joseph

Combined Drainage and Protocolized Necrosectomy Through a Coaxial Lumen-apposing Metal Stent for Pancreatic Walled-off Necrosis: A Prospective Multicenter Trial.

通过同轴管腔放置金属支架联合引流和方案坏死切除术治疗胰腺封闭性坏死：一项前瞻性多中心试验。

• DOI: 10.1097/sla.0000000000005274
• 发表时间: 2023
• 期刊: Annals of surgery
• 影响因子: 9
• 作者: Dayyeh,BarhamKAbu;Chandrasekhara,Vinay;Shah,RajJ;Easler,JeffreyJ;Storm,AndrewC;Topazian,Mark;Levy,MichaelJ;Martin,JohnA;Petersen,BretT;Takahashi,Naoki;Edmundowicz,Steven;Hammad,Hazem;Wagh,MihirS;Wani,Sachin;DeWitt,Joh
• 通讯作者: DeWitt,Joh