TREATMENT OF METABOLIC PRURITIS

代谢性瘙痒症的治疗

• 批准号: 7377616
• 负责人: MARLYN J MAYO
• 金额: $ 0.5万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377616
• 关键词: TREATMENT; METABOLIC; PRURITIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pruritus is a hallmark feature of cholestatic liver diseases and is estimated to occur in 20%-50% of patients with jaundice and 70%-80% of patients with primary biliary cirrhosis (PBC). Pruritus significantly affects quality of life and can lead to chronic sleep deprivation. Currently used therapies are often ineffective and/or poorly tolerated. Only a few have been examined in the setting of controlled trials. Practice guidelines issued by the American Association for the Study of Liver Diseases state that the first line of therapy for cholestatic pruritus is bile acid binding resins such as cholestyramine. Bile acid binding resins can be partially effective in up to 85% of patients, but compliance tends to be poor because the preparation is unpalatable. In addition, these resins avidly bind to and prevent absorption of almost all other medications, severely restricting the medical management of the patients. The second line of therapy is rifampicin, which has been shown to be modestly effective in several small trials. The major problem with rifampicin is that it leads to increases in serum bilirubin levels. Serum bilirubin is the single most important predictor of survival in patients with PBC, and thus rifampicin therapy impairs the physician's ability to follow the patient's course. In addition, there have been reports of rifampicin-induced hepatitis, which could pose a serious problem in patients with already limited liver function. The third line therapies are all considered experimental because they either have unproved efficacy and/or severely limiting side effects. They include: opioid receptor blockers, which are unpleasant because they result in an opioid withdrawal-like syndrome in PBC patients; phenobarbitol and propofol, which are heavily sedating; anti-histamines, which are not very effective and also worsen the xerostomia of sicca syndrome that is present in 80% of patients with PBC and many patients with hepatitis C (HCV); s-adenosylmethionine (SAMe, a dietary supplement), phototherapy; anti-convulsants, ondansetron, and plasmapheresis. Intractable cholestatic pruritus is considered a valid indication for liver transplantation in the absence of overt hepatocellular failure, an effective but drastic and costly measure. In rare cases, patients have opted for suicide in order to avoid the constant distress of unmanageable pruritus. The broad, long-term objective of this project is to improve the health and quality of life of patients with systemic diseases that cause pruritus. The hypothesis of this project, which is based on our 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. This particular study is intended to serve as a feasibility and dose-finding pilot trial to determine the tolerability and effective dose of sertraline as a treatment for cholestatic pruritus. It is anticipated that this pilot trial will be followed by a larger, double-blind, randomized, placebo-controlled trial to definitively evaluate the efficacy sertraline therapy for pruritus.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。瘙痒是胆汁淤积性肝病的标志性特征，估计在20％-50％的黄疸患者和70％-80％的原发性胆道肝硬化患者（PBC）中发生。瘙痒会显着影响生活质量，并可能导致长期睡眠剥夺。当前使用的疗法通常无效和/或耐受性不佳。在对照试验的设置中，只有少数几个。美国肝病研究协会发布的实践指南指出，胆汁淤积性瘙痒的第一线是胆汁酸结合树脂，例如胆固醇。胆汁酸结合树脂在多达85％的患者中可以部分有效，但是依从性往往很差，因为制剂是不可能的。此外，这些树脂与几乎所有其他药物的吸收都非常限制，严重限制了患者的医疗管理。第二道治疗是利福平，在几个小试验中已显示出适度的有效性。利福平的主要问题是，它导致血清胆红素水平升高。血清胆红素是PBC患者生存的最重要预测指标，因此利福平疗法损害了医生遵循患者病程的能力。此外，还有关于利福平诱导的肝炎的报道，这可能在肝功能有限的患者中构成严重问题。第三行疗法都被认为是实验性的，因为它们具有未证实的功效和/或严重限制副作用。它们包括：阿片类药物受体阻滞剂，这是令人不愉快的，因为它们会导致PBC患者的阿片类药物戒断样综合征；苯巴苄醇和丙泊酚，它们镇静了；抗抗药性不是很有效，并且也使SICCA综合征的静态症恶化，其中80％的PBC患者和许多丙型肝炎患者（HCV）存在； S-腺苷硫氨酸（相同，饮食补充剂），光疗；抗惊厥药物，onDansetron和血浆置换。在没有明显的肝细胞衰竭的情况下，顽固性胆固性瘙痒被认为是肝移植的有效指征，这是一种有效但昂贵的测量。在极少数情况下，患者选择了自杀，以避免持续不可控制的瘙痒。 该项目的广泛长期目标是改善引起瘙痒的全身性疾病患者的健康和生活质量。该项目的假设是基于我们以前的观察结果，即一些PBC患者在给予舍曲林时已经解决了其瘙痒，这是舍曲林治疗将改善胆汁淤积性瘙痒的症状。这项特定的研究旨在作为可行性和剂量调查试验试验，以确定舍曲林的耐受性和有效剂量作为胆汁淤积性瘙痒的治疗方法。预计该试验试验将在较大，双盲，随机，安慰剂对照试验之后，以确定评估瘙痒症的疗效舍曲林治疗。