HIGH DOSE UDCA FOR PRIMARY SCLEROSING CHOLANGITIS

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。 本研究旨在探讨大剂量熊去氧胆酸(UDCA)治疗原发性硬化性胆管炎(PSC)的安全性和有效性。 PSC是一种原因不明的慢性肝病。它的特点是炎症和肝(肝)胆管的破坏。这种疾病进展缓慢，通常会在10-15年内导致肝硬化、高血压和肝功能衰竭。PSC是美国成年人最常见的肝病之一，也是肝移植的重要适应症。PSC的原因尚不清楚。在至少70%的病例中，PSC与炎症性肠病和溃疡性结肠炎有关。目前还没有关于PSC的有效药物治疗的报道。传统的肝病治疗方法在治疗PSC方面尚未被证明有效。毒性胆汁酸蓄积可能是PSC损伤的重要机制之一。因此，在PSC治疗中使用UDCA的理由包括有证据表明它具有免疫调节作用，并用毒性较低的胆汁酸(UDCA)取代胆汁酸。在对PSC患者的一项试点研究中，UDCA在24个月的治疗中改善了肝酶。另一项小型试验在那些接受UDCA治疗的患者中产生了组织改善。一项更大规模的随机研究显示，治疗或死亡终点没有显著变化，然而，UDCA的剂量很小。 这项研究的目的是确定较大剂量的UDCA治疗PSC是否有效。患者将接受至少四年的随访研究，以确定大剂量UDCA的长期影响。A主题访问将在GCRC举行。所有受试者都将接受体检、血液测量和组织样本采集。此外，还可以进行其他常规诊断测试。患者将被要求签署单独的同意书才能进行任何额外的手术。在这项研究期间进行的所有测试都将根据治疗PSC患者的护理标准进行。数据将被用来确定大剂量UDCA对PSC患者的有效性。

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. The purpose of the research study is to determine the safety and effectiveness of high doses of Ursodiol, a ursodeoxycholic acid (UDCA), in the treatment of primary sclerosing cholangitis (PSC). PSC is a chronic liver disease of unknown cause. It is characterized by inflammations and destruction of the hepatic (liver) bile ducts. The disease is slowly progressive and usually leads to cirrhosis, hypertension and liver failure over a 10-15 year period. PSC is one of the most common liver diseases and an important indication for liver transplantation in US adults. The cause of PSC is unknown. In at least 70% of the cases, PSC is associated with inflammatory bowel disease and ulcerative colitis. There are no reports of effective medical therapy for PSC at this time. Traditional treatments for liver disease have not been proven effective in the treatment of PSC. The accumulation of toxic bile acids may be an important mechanism of injury in PSC. Therefore, the rationale for using UDCA in the treatment of PSC includes evidence that it plays an immune modifying role and replaces the bile acid with a less toxic bile acid (UDCA). In a pilot study of patients with PSC, UDCA improved liver enzymes over 24 months of treatment. Another small trial produced tissue improvements in those treated with UDCA. A larger randomized study showed no significant changes in treatment or death endpoints, however, the dose of UDCA was small. The purpose of this study is to determine if treatment with higher doses of UDCA is effective in the treatment of PSC. Patients will be studies for a minimum of four years of follow-up to determine the long term effects of high doses of UDCA. A subjects visits will be held in the GCRC. Medical and physical examinations, blood measurements, and tissue sample collection will be done for all subjects. In addition, other routine diagnostic tests may be performed. Patients will be required to sign separate consent forms for any additional procedures. All tests done during this study will be done according to the standard of care for treatment of patients with PSC. Data will be used to determine the effectiveness of UDCA in high doses for patients with PSC.