Multicentered Randomized Trail of High-dose Urso in PSC

高剂量 Urso 在 PSC 中的多中心随机试验

• 批准号: 6649226
• 负责人: Keith D Lindor
• 金额: $ 55.88万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6649226
• 关键词: biliary tract disorder chemotherapy; clinical research; clinical trials; dosage; drug screening /evaluation; histopathology; human subject; human therapy evaluation; liver cirrhosis; pathologic process; patient oriented research; primary sclerosing cholangitis; ursodeoxycholate

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.

描述（由申请人提供）： 原发性硬化性胆管炎（PSC）是一种进行性慢性胆汁淤积性肝脏 通常与慢性结肠炎有关的未知病因疾病。 PSC是成年人中常见的肝病，通常会导致晚期肝脏 疾病和肝衰竭，因此是肝脏的重要迹象 移植。不幸的是，目前尚无有效的医疗疗法 对于PSC。研究人员组有临床的长期记录 慢性胆汁淤积性肝病的试验，特别是在原发性硬化中 胆管炎。最近，我们从一项试点研究中产生了有希望的结果 在PSC的治疗中，使用高剂量的ursdexycholic酸。较低剂量 PSC患者的ursdexycholic酸的生化改善，但 在先前的研究中不影响其他临床上重要的终点。我们的 飞行员数据由来自小的小组的数据支持 高剂量的ursdexyoxycholic酸导致生化的随机试验 与安慰剂相比，组织学和胆管造影的改善在两年后。 在此提交中，我们提出了一个大规模的多中心安慰剂对照 150例患者 原发性硬化性胆管炎。研究的主要终点将包括 组织学向肝硬化，食管或胃的发展 静脉曲张，需要肝移植和存活。次要端点将 包括测量尿脱氧胆酸（28-30 mg/kd/d）的影响 肝生物化学，组织学阶段，胆管造影特征，蛋黄酱风险 使用经过验证的问卷调查得分和生活质量。这项研究将是 有史以来最大的PSC和后续行动将是最广泛的。 这将为研究的自然历史提供宝贵的资源 这种疾病，作为本研究的一部分，我们还将收集血清，细胞 从肝脏和结肠中提取DNA，胆汁和组织作为资源 未来的研究。该试验的以上为中心的性质将允许招募 来自多样化患者人群的患者进入这项研究，代表 这种疾病的性别和种族分布。成功的机会 大量的PSC患者人群增强了这项研究的完成 参与中心目前管理，认可这些网站 PSC的新患者的推荐中心以及长期的轨道 胆汁淤积性肝病的临床试验记录。