Biliary Microlithiasis in Alcohol Induced Pancreatitis

酒精性胰腺炎中的胆道微石症

• 批准号: 7103146
• 负责人: ARUN J SANYAL
• 金额: $ 20.58万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103146
• 关键词: acute disease /disorder; alcoholic beverage consumption; alcoholism /alcohol abuse; amylases; bile obstruction; biliary tract disorder chemotherapy; blood tests; cholangiography; cholecystokinin; cholelithiasis; clinical research; clinical trial phase II; comorbidity; drug screening /evaluation; human subject; human therapy evaluation; lipase; pancreas imaging /visualization; pancreatitis; pathologic process; patient oriented research; questionnaires; ultrasound; ursodeoxycholate

DESCRIPTION (provided by applicant): Alcohol-induced pancreatitis is often characterized by repeated flares of acute pancreatitis and the eventual development of exocrine and endocrine pancreatic failure. Once chronic pancreatitis develops, there is no established way to predictably slow down the progression of the disease. In preliminary studies, it has been observed that a substantial proportion of subjects with alcohol-induced pancreatitis have biliary microlithiasis. Biliary microlithiasis has been implicated as a cause of idiopathic acute recurrent pancreatitis. Based on the preliminary observations and the known role of biliary microlithiasis in pancreatitis, it is hypothesized biliary microlithiasis is frequently present in subjects with alcohol-induced pancreatitis and that its dissolution with urosodeoxycholic acid (UDCA) will ameliorate the acute flares of pancreatitis and slow down the progression to pancreatic failure. This R21 exploratory grant proposal represents the first step towards testing this novel hypothesis and has two major objectives: (1) to define the prevalence and types of biliary microlithiasis in subjects with alcohol-induced pancreatitis, and (2) to provide "proof of concept" that UDCA can clear the bile of microlithiasis in subjects with alcohol-induced pancreatitis and identify the factors associated with successful clearance of microlithiasis. These will be accomplished by studies with two specific aims: (1) to define the prevalence and types of biliary microlithiasis in subjects with alcohol-induced pancreatitis and (2) to perform a PHASE II pilot study of UDCA (10 mg/kg/day) to define its biologic effectiveness for clearance of microlithiasis in subjects with alcohol-induced pancreatitis and biliary microlithiasis. This will be accomplished using a double-blind, placebo-controlled, randomized study design. The primary endpoint will be the absence of biliary microlithiasis, defined by microscopic examination of bile obtained from the duodenum after cholecystokinin injection at study termination at 6 months. Secondary endpoints will include (1) subset analysis to identify which types of microlithiasis are dissolved by UDCA, (2) identify factors associated with dissolution of microlithiasis, (3) changes in bile composition over time, (4) frequency of flares of pancreatitis, and (4) the tolerability of UDCA, Axcan Pharma, has kindly agreed to provide the drug and placebo free of cost to the study. The long-term goal is to use data from this R21 proposal to develop a RO1 proposal about a large scale phase III clinical trial of UDCA for alcohol-induced pancreatitis.

描述（由申请人提供）：酒精诱发的胰腺炎通常以急性胰腺炎反复发作以及最终发展为外分泌和内分泌胰腺衰竭为特征。一旦发生慢性胰腺炎，就没有既定方法可以可预测地减缓疾病的进展。初步研究发现，相当比例的酒精性胰腺炎患者患有胆道微石症。胆道微石症被认为是特发性急性复发性胰腺炎的病因。根据初步观察和胆道微石症在胰腺炎中的已知作用，推测胆道微石症 微石症经常出现在酒精诱发的胰腺炎患者中，用尿去氧胆酸（UDCA）溶解微石症将改善胰腺炎的急性发作并减缓胰腺衰竭的进展。这项 R21 探索性拨款提案代表了检验这一新假设的第一步，有两个主要目标：(1) 确定酒精性胰腺炎受试者中胆道微石症的患病率和类型，(2) 提供“概念证明” “UDCA 可以清除酒精诱发的胰腺炎受试者的胆汁中的微石症，并确定与成功清除微石症相关的因素。 这些将通过具有两个具体目标的研究来完成：(1) 确定酒精性胰腺炎受试者中胆道微石症的患病率和类型，以及 (2) 进行 UDCA（10 毫克/公斤/天）的 II 期试点研究）以确定其清除酒精性胰腺炎和胆道微石症受试者中微石症的生物学有效性。这将通过双盲、安慰剂对照、随机研究设计来完成。主要终点是不存在胆道微石症，通过在 6 个月研究终止时注射缩胆囊素后对十二指肠获取的胆汁进行显微镜检查来定义。次要终点将包括 (1) 子集分析，以确定 UDCA 溶解了哪些类型的微石症，(2) 确定与微石症溶解相关的因素，(3) 胆汁成分随时间的变化，(4) 胰腺炎发作的频率， (4) UDCA 的耐受性，Axcan Pharma 已同意免费为该研究提供药物和安慰剂。长期目标是利用此 R21 提案中的数据制定 RO1 提案，涉及 UDCA 治疗酒精性胰腺炎的大规模 III 期临床试验。