Multicentered Randomized Trail of High-dose Urso in PSC

描述(由申请人提供)： 原发性硬化性胆管炎(PSC)是一种进行性慢性淤胆性肝脏 病因不明的疾病，通常与慢性结肠炎有关。 PSC是成人常见的肝病，通常会导致肝脏进展期。 疾病和肝功能衰竭，因此是肝脏的一个重要适应症。 移植。不幸的是，目前还没有有效的药物治疗方法。 对于PSC。这组研究人员有长期的临床记录 慢性淤胆性肝病的试验，特别是在原发性硬化方面 胆管炎。最近，我们从一项初步研究中获得了令人振奋的结果。 大剂量熊去氧胆酸治疗PSC较低剂量 熊去氧胆酸在PSC患者中的应用导致生化改善 在先前的研究中没有影响其他临床重要的终点。我们的 试点数据由来自另一组的数据支持， 随机试验高剂量熊去氧胆酸导致生化， 两年后，与安慰剂相比，组织学和胆道造影术都有改善。 在这份意见书中，我们提出了一项大规模多中心安慰剂对照研究 150例患者的随机试验，至少随访4年 原发性硬化性胆管炎。这项研究的主要终点包括 组织学进展为肝硬变、食道或胃的发展 静脉曲张，肝移植的需要，以及生存。次要终端将 包括测量尿脱氧胆酸(28-30 mg/kd/d)对 肝脏生化、组织学分期、胆道造影特征、Mayo风险 得分和生活质量，使用经过验证的问卷。这项研究将是 这是PSC有史以来规模最大的一次，后续行动将是最广泛的。 这将为研究中国的自然历史提供宝贵的资源。 作为这项研究的一部分，我们还将收集血清、细胞 从肝脏和结肠中提取DNA、胆汁和组织作为来源 未来的研究。这项试验的多中心性质将允许招募 从不同的患者群体进入这项研究，具有代表性 这种疾病的性别和种族分布。成功的机会 这项研究的完成是因为大量的PSC患者群体 参与中心目前管理，承认这些地点为 PSC新患者的转诊中心，以及长期的跟踪 胆汁淤积性肝病的临床试验记录。

DESCRIPTION (provided by applicant): Primary sclerosing cholangitis (PSC) is a progressive chronic cholestatic liver disease of unknown etiology that is commonly associated with chronic colitis. PSC, a common liver disease among adults, usually leads to advanced liver disease and liver failure, and as such, is an important indication for liver transplantation. Unfortunately, no effective medical therapy currently exists for PSC. The group of investigators has a longstanding track record of clinical trials in chronic cholestatic liver disease, particularly in primary sclerosing cholangitis. Recently we have generated promising results from a pilot study using high doses of ursodeoxycholic acid in the treatment of PSC. Lower doses of ursodeoxycholic acid in patients with PSC led to biochemical improvement but did not affect other clinically important endpoints in a previous study. Our pilot data is supported by data from another group showing in a small, randomized trial that high dose ursodeoxycholic acid led to biochemical, histologic, and cholangiographic improvement compared to placebo at two years. In this submission, we propose a large-scale multi-center placebo-controlled randomized trial with a minimum follow-up of four years for 150 patients with primary sclerosing cholangitis. Primary endpoints of the study will include histologic progression to cirrhosis, development of esophageal or gastric varices, need for liver transplantation, and survival. Secondary endpoints will include measurements of the effects of urosodeoxycholic acid (28-30 mg/kd/d) on liver biochemistries, histologic stage, cholangiographic features, Mayo risk score, and quality of life, using validated questionnaires. This study will be the largest ever conducted in PSC and the follow-up will be the most extensive. This will provide an invaluable resource for studying the natural history of this disease and as part of this study we will also collect serum, cells for extraction of DNA, bile, and tissue from the liver and colon as a resource for future studies. The multi-centered nature of this trial will allow recruitment of patients into this study from a diverse patient population, representative of the gender and racial distribution of this disease. Chances of successful completion of this study are enhanced by the large PSC patient population that the participating centers currently manage, recognition of these sites as referral centers for new patients with PSC, as well as a longstanding track record in clinical trials in cholestatic liver disease.