1Treatment of Cholestatic Pruritus With Sertraline

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性肝硬化（PBC）和其他引起瘙痒症的疾病患者的健康和生活质量。本提案的近期目标是确定舍曲林治疗胆汁淤积性瘙痒症的安全性和有效性。该建议的假设是基于先前的观察，即一些PBC患者在给予舍曲林后瘙痒消退，舍曲林治疗将改善胆汁淤积性瘙痒的症状。具体目标是：1）确定舍曲林治疗胆汁淤积性瘙痒的最佳剂量和反应时间2）确定舍曲林在肝功能降低患者中的耐受性。本提案的次要目的是评价舍曲林对胆汁淤积性瘙痒症的影响，并确定瘙痒症的变化与抑郁症状或血浆舍曲林/去甲基舍曲林水平的变化之间的关系。该项目的健康相关性是确定一种创新的、更有效的、耐受性更好的胆汁淤积性瘙痒症治疗方法的潜力。胆汁淤积性肝病患者常伴有致残性瘙痒。目前的治疗并不总是有效的，有时需要肝移植来缓解瘙痒。慢性瘙痒症显著损害生活质量。该提案中使用的方法是舍曲林在PBC或慢性丙型肝炎所致瘙痒患者中的临床治疗试验。研究设计分为两个部分。在第一部分（A）中，患有胆汁淤积性瘙痒症的受试者将接受舍曲林的非盲剂量递增。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。将收集和分析关于舍曲林的瘙痒症状和副作用的数据，以确定舍曲林在这种情况下使用的安全性和有效性。这些研究将作为试点试验。该拟议项目的结果将用于设计一项更大的对照试验，该试验可通过R 01机制申请资助。

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.