1Treatment of Cholestatic Pruritus With Sertraline

1舍曲林治疗胆汁淤积性瘙痒症

• 批准号: 6728266
• 负责人: MARLYN J MAYO
• 金额: $ 15.6万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6728266
• 关键词: biliary tract disorder chemotherapy; clinical research; clinical trials; depression; drug adverse effect; drug screening /evaluation; hepatitis C; human subject; human therapy evaluation; liver function; patient oriented research; pharmacokinetics; primary biliary cirrhosis; pruritis; psychological tests; quality of life; sertraline; sign /symptom

DESCRIPTION (provided by applicant): The broad, long-term objective of this proposal is to improve the health and quality of life of patients with primary biliary cirrhosis (PBC) and other disorders that cause pruritus. The immediate, short-term objective of this proposal is to determine the safety and efficacy of sertraline as a treatment for cholestatic pruritus. The hypothesis of this proposal, which is based on the previous observation that some patients with PBC have experienced resolution of their pruritus when given sertraline, is that sertraline therapy will improve the symptom of cholestatic pruritus. The specific aims are: 1) to determine the optimal dose and time to response of sertraline treatment for cholestatic pruritus 2) to determine the tolerability of sertraline in patients with reduced liver function. The secondary aims of this proposal will be to evaluate the effect of sertraline on cholestatic pruritus and to determine how changes in pruritus are related to changes in depressive symptoms or plasma sertraline/desmethylsertraline levels. The health relatedness of the project is the potential to identify an innovative, more effective, and better-tolerated treatment of cholestatic pruritus. Patients with cholestatic liver disease often suffer from disabling pruritus. Current treatments are not always effective, and liver transplantation is sometimes necessary to alleviate the pruritus. Quality of life is significantly impaired by chronic pruritus. The method to be used in the proposal is a clinical therapeutic trial of sertraline in patients with pruritus due to either PBC or chronic hepatitis C. The research design is divided into two parts. In first part (A), subjects with cholestatic pruritus will undergo an unblinded dose escalation of sertraline. Part B of the study will consist of a double-blind, randomized, placebo-controlled, crossover study of the efficacy of sertraline. Data regarding pruritus symptoms and side effects of sertraline will be collected and analyzed to determine the safety and efficacy of sertraline used in this setting. These studies will serve as pilot trials. The results of this proposed project will be used to design a larger controlled trial that could be proposed for funding through an R01 mechanism.

描述（由申请人提供）： 该提案的广泛长期目标是改善原发性胆汁肝病（PBC）患者的健康和生活质量和其他引起瘙痒的疾病。该提案的直接，短期目标是确定舍曲林作为胆汁淤积的治疗方法的安全性和功效。该提案的假设是基于先前的观察结果，即在给予舍曲林时，一些PBC患者已经解决了瘙痒，这是舍曲林治疗将改善胆汁淤积性瘙痒的症状。具体目的是：1）确定舍曲林治疗胆汁淤积性瘙痒的最佳剂量和时间2）确定舍曲林在肝功能降低的患者中的耐受性。该提案的次要目的是评估舍曲林对胆汁淤积的影响，并确定瘙痒的变化如何与抑郁症状或血浆舍曲林/脱甲基甲肾上腺素水平的变化有关。该项目的健康相关性是有潜力确定胆汁淤积性的创新，更有效，更耐受的治疗方法。胆汁淤积性肝病的患者经常患有瘙痒。当前的治疗并不总是有效的，有时需要肝移植来减轻瘙痒。慢性瘙痒会严重损害生活质量。该提案中要使用的方法是针对PBC或慢性丙型肝炎引起的瘙痒患者的舍曲林的临床治疗试验。研究设计分为两部分。在第一部分（a）中，患有胆汁淤积的受试者将接受舍曲林的无盲剂量升级。该研究的B部分将包括双盲，随机，安慰剂对照的舍曲林疗效的跨界研究。将收集和分析有关舍曲林症状和副作用的数据，以确定在这种情况下使用的舍曲林的安全性和功效。这些研究将作为试点试验。该提议的项目的结果将用于设计一个更大的对照试验，该试验可以通过R01机制提出资金。