1Treatment of Cholestatic Pruritus With Sertraline

描述(由申请人提供)： 这项建议的广泛和长期目标是改善原发性胆汁性肝硬变(PBC)和其他引起瘙痒的疾病患者的健康和生活质量。这项建议的近期、短期目标是确定舍曲林治疗胆汁淤积性瘙痒的安全性和有效性。这一建议的假设是基于先前的观察，即一些PBC患者在服用舍曲林时他们的瘙痒症状得到了缓解，即舍曲林治疗将改善胆汁淤积性瘙痒的症状。其具体目的是：1)确定舍曲林治疗淤胆性瘙痒的最佳剂量和起效时间；2)确定舍曲林在肝功能减退患者中的耐受性。这项建议的次要目的将是评估舍曲林对胆汁淤积性瘙痒的疗效，并确定瘙痒的变化如何与抑郁症状或血浆舍曲林/去甲基舍曲林水平的变化有关。该项目的健康相关性在于有可能确定一种创新的、更有效的、耐受性更好的胆汁淤积性瘙痒治疗方法。胆汁淤积性肝病的患者通常会出现致残性瘙痒。目前的治疗方法并不总是有效的，有时需要进行肝移植来缓解瘙痒。慢性瘙痒会严重影响患者的生活质量。建议中使用的方法是舍曲林对PBC或慢性丙型肝炎引起的瘙痒患者的临床治疗试验。研究设计分为两部分。在第一部分(A)中，胆汁淤积性瘙痒的受试者将接受舍曲林的无盲目剂量递增。该研究的B部分将包括舍曲林疗效的双盲、随机、安慰剂对照、交叉研究。将收集和分析舍曲林的瘙痒症状和副作用的数据，以确定舍曲林在该环境中使用的安全性和有效性。这些研究将作为试点试验。这一拟议项目的结果将用于设计一项更大规模的对照试验，可以通过R01机制提出资金。

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.