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 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功能丧失 和使腹痛使人衰弱。尚不清楚为什么有些人会进展和发展并发症， 包括胰腺生成糖尿病（PDM）和/或胰腺癌（PDAC）。在这个财团中，调查员 提出有关风险因素，环境影响和概念证明的驱动率研究的建议 研究领域向前发展的研究，尤其是那些增加PDM和PDAC风险的因素。我们 提议以下具体目标（SA）来满足RFA-DK-14-027的目标。 SA＃1：定义自然 患有CP或急性复发性胰腺炎的小儿和成年患者的病史，我们 提案一项前瞻性观察队列研究。我们将重点放在确定风险因素和 患有PDM和/或PDAC的患者的表型。生物标本将获得 促进可能促进早期疾病诊断和管理的可能生物标志物的研究。 SA ＃2：PDM的发病机理以及非内分泌胰腺疾病与胰岛功能障碍的相互作用 不太了解。我们将使用胰岛功能的测量（口服葡萄糖耐量测试，精氨酸 - 在横截面和前瞻性研究中增强高血糖夹），以定义患病率和 CP中代谢失调和糖尿病的生理基础。我们还将前景确定变化 在胰岛功能和向公开PDM的过渡中，并将代谢状态的变化与变化相关联 胰腺炎症和功能。 SA＃3：评估磁共振的诊断效率（MR） 在对可疑早期CP的非侵入性评估中进行成像，我们提出了一项比较CP的前瞻性研究 患有胰腺外分泌功能正常的对照人群的患者。降低的T1加权MR信号， 响应促进蛋白刺激的扩散减少和十二指肠液体积减少可能表明CP。 SA＃4：Galectin-3（Gal-3）是一种碳水化合物结合蛋白，似乎参与纤维发生和 CP中的组织重塑。 GAL-3抑制剂似乎是安全的，并且显示出减少器官纤维化的潜力 人类。为了确定GAL-3抑制剂的安全性和效率，我们提出了一个随机的安慰剂 66例CP患者的对照试验。疗法后十二指肠液碳酸氢盐水平的改善将是 一级效率终点。我们预计这种药物会逆转纤维化，这表现为改善 十二指肠碳酸氢盐水平。其他终点包括MRI/MRCP外观，GAL-3水平，生活质量， 还将评估腹痛评分和β细胞功能。

项目成果

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

• 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

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

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

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