A PHASE II TRIAL OF URSODEOXYCHOLIC ACID (UDCA) THERAPY FOR BILIARY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 酒精性胰腺炎是一种以急性胰腺炎反复发作为特征的慢性致残性疾病。这些反复发作的耀斑背后的病理生理机制(S)尚不完全清楚。在初步研究中，55%的酒精性胰腺炎患者入院时有剧烈的腹痛，发现有胆道微结石。已知胆道微石症在特发性复发性胰腺炎患者中非常普遍(1；2)。在这一人群中，胆道微结石的溶解减少了胰腺炎急性发作的频率。 在此基础上，提出了以下新的假设： 胆道微结石存在于部分酒精性胰腺炎患者中，并导致此类患者急性胰腺炎反复发作。因此，其与熊去氧胆酸(UDCA)的溶解将减少该人群中急性胰腺炎发作的频率。 这项R21提案有两个主要目标，这是检验这一假设的第一步。它们是： 1.明确酒精性胰腺炎患者胆道微结石的患病率和类型 具体目标1：明确酒精性胰腺炎受试者各种类型胆管微结石的现患率。 2.提供UDCA可以清除酒精性胰腺炎患者胆汁微结石的概念证据，并确定与微结石清除成功相关的因素。 具体目的2：进行UDCA(10 mg/kg/d)的II期先导性研究，以确定其清除酒精性胰腺炎和胆道微结石患者胆道微结石的生物学有效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcohol-induced pancreatitis is a chronic and disabling condition characterized by recurrent flares of acute pancreatitis. The pathophysiologic mechanism(s) underlying these recurrent flares are not fully known. In preliminary studies, 55% of subjects with alcohol-induced pancreatitis admitted with a flare of abdominal pain were found to have biliary microlithiasis. Biliary microlithiasis is known to be highly prevalent in those with idiopathic recurrent pancreatitis (1;2). Dissolution of biliary microlithiasis reduces the frequency of acute attacks of pancreatitis in this population. Based on these, the following novel hypothesis is proposed: Biliary microlithiasis is present in a subset of subjects with alcohol-induced pancreatitis and contributes to recurrent flares of acute pancreatitis in such patients. Therefore, its dissolution with urso-deoxycholic acid (UDCA) will reduce the frequency of acute flares of pancreatitis in this population. There are two main objectives of this R21 proposal which are the first steps to testing this hypothesis. These are: 1. TO DEFINE THE PREVALENCE AND TYPES OF BILIARY MICROLITHIASIS IN SUBJECTS WITH ALCOHOL-INDUCED PANCREATITIS Specific Aim 1: To define the point prevalence of various types of biliary microlithiasis in subjects with alcohol-induced pancreatitis. 2. TO PROVIDE 'PROOF OF CONCEPT' THAT UDCA CAN CLEAR THE BILE OF MICRO-LITHIASIS IN SUBJECTS WITH ALCOHOL-INDUCED PANCREATITIS AND IDENTIFY THE FACTORS ASSOCIATED WITH SUCCESSFUL CLEARANCE OF MICROLITHIASIS Specific Aim 2: To perform a PHASE II PILOT study of UDCA (10 mg/kg/day) to define its biologic effectiveness for clearance of biliary microlithiasis in subjects with alcohol-induced pancreatitis and biliary microlithiasis.