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的反复发作和最终发育外分泌和内分泌胰腺衰竭的发展。一旦慢性胰腺炎发展出来，就无法预测地降低疾病进展。在初步研究中，已经观察到，患有酒精诱导的胰腺炎的受试者很大一部分患有胆道小石病。胆道微石质已被认为是特发性急性复发性胰腺炎的原因。基于初步观察和胆道微石症在胰腺炎中的已知作用，它是假设的胆汁 微石症经常存在于患有酒精诱发的胰腺炎的受试者中，并且其用尿脱氧胆酸（UDCA）溶解会改善胰腺炎的急性叶子，并减缓胰腺衰竭的进展。这项R21探索性赠款提案是测试这一新假设的第一步，并具有两个主要目标：（1）在患有酒精引起的胰腺炎的受试者中定义胆汁型小石症的流行和类型微石录。 这些将通过具有两个具体目的的研究来完成：（1）在患有酒精诱导的胰腺炎受试者中定义胆道小石症的患病率和类型，以及（2）对UDCA（10 mg/kg/day）进行II期试验研究（10 mg/kg/day），以确定其在与酒精际炎和BILIS炎的小石症中的生物学有效性和billity炎的生物学作用。这将使用双盲，安慰剂对照，随机研究设计来实现。主要终点将是缺乏胆道微石质，这是通过对胆囊基蛋白在6个月时从十二指肠上获得的胆汁进行的微观检查定义的。次级终点将包括（1）子集分析，以确定UDCA溶解了哪些类型的微石病，（2）确定因子溶解相关的因素，（（3）胆汁成分随时间的变化，（4）胰腺炎的频率，以及（4）（4）UDCA，AXCAN PHARMAS的宽松性，可及时提供药物，并提供了供应的药物，并提供了构成的位置和地位。长期的目标是使用该R21提案中的数据来开发有关UDCA对酒精诱导的胰腺炎的大规模III期临床试验的RO1提案。