Baltimore VIRAHEP-C Clinical Center

巴尔的摩 VIRAHEP-C 临床中心

• 批准号: 6895112
• 负责人: CHARLES D HOWELL
• 金额: $ 10.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-21 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895112
• 关键词: African American; caucasian American; chronic disease /disorder; clinical research; clinical trials; combination chemotherapy; cooperative study; drug resistance; genetic susceptibility; hepatitis C; human subject; human therapy evaluation; immunotherapy; interferon alpha; liver disorder chemotherapy; patient oriented research; pharmacogenetics; prognosis; racial /ethnic difference; ribavirin; virus genetics; virus load

DESCRIPTION (provided by applicant): Hepatitis C (HCV) is the most common cause for chronic liver disease and cirrhosis in the United States, affecting three million U.S residents and causing 8-10 thousand deaths annually. The number of deaths per year due to chronic HCV is projected to triple by 2010-2015, as individual infected during the peak incidence of infection develop end-stage liver cirrhosis. HCV infection is two times mores prevalent in African Americans than White Americans. Furthermore, African Americans appear to have worse outcome, with a higher incidence of primary hepatocellular carcinoma (HCC) and higher death rates due to cirrhosis and HCC. Few African Americans have beer enrolled in clinical trials of HCV therapies. Yet the available data shows significantly lower rates of HCV clearance long-term following interferon alfa (IFN) therapies alone and IFN combined with ribavirin (RBV), compared to White Americans. The lower efficacy of antiviral therapies in African Americans is due, in part, to a higher prevalence of infection with HCV genotype 1 (HCV-1). Yet-the long term clearance of HCV adjusted for HCV genotype is still lower in African American patients, suggesting a potentially important role for host factors in determining the lower treatment response rates. There is a critical need for multicenter clinical trials with adequate numbers of African Americans to conclusively determine the efficacy of combination antiviral therapy for chronic HCV in African Americans and to define the host and viral mechanisms that form the basis for the racial differences in treatment outcomes. Thus, we propose the Baltimore Clinical Center to participate in a multicenter clinical study of resistance to antiviral therapies for chronic HCV-1(VIRAHEP-C). The long-term objective of this award is to identify effective antiviral treatment(s) for African Americans infected with HCV-1. The projects has four Specific Aims: I) Determine the rates of sustained virological response to a 48 week course of combination antiviral therapy, among non-Hispanic, African American and non-Hispanic, White American chronic HCV-1 patients; 2) Determine which host and viral factors predict a sustained virological response to combination antiviral therapy in non-Hispanic, African American and non-Hispanic, White American chronic HCV-I patients; 3) Determine the patterns of HCV (RNA) kinetics in African American and Caucasian chronic. HCV-1 patients during antiviral therapy; 4) Determine whether early HCV (RNA) kinetics accurately predicts the end of treatment and sustained virological responses in African-American and Caucasian chronic HCV-I patients following antiviral therapy. In collaboration with ancillary studies, this project will investigate the influence of selected viral and host factors on the efficacy of treatment for chronic HCV. These studies may provide important new insights into the pathogenesis of HCV and lead to novel therapies for chronic HCV.

描述（由申请人提供）： 丙型肝炎（HCV）是慢性肝病和 美国的肝硬化，影响了300万美国居民， 每年造成8-10,000人死亡。每年由于 慢性HCV预计到2010-2015将在三倍之前被感染 感染的峰值发病率会发展出末期肝肝硬化。 HCV 在非洲裔美国人中，感染是两倍，而不是白人 美国人。此外，非裔美国人似乎的结果较差，有一个 原发性肝细胞癌（HCC）和较高死亡的发病率更高 肝硬化和HCC的速率。很少有非洲裔美国人参加啤酒 HCV疗法的临床试验。然而，可用的数据大大显示 干扰素阿尔法（IFN）长期长期HCV清除率较低（IFN） 与白色相比 美国人。非裔美国人抗病毒药疗法的效力较低是 由于HCV基因型1（HCV-1）的感染率较高，部分原因是由于感染率较高。 尚未为HCV基因型调整的HCV的长期清除率仍然较低 非洲裔美国患者，这表明宿主起着潜在的重要作用 确定较低治疗反应率的因素。有关键 需要足够数量的非裔美国人的多中心临床试验 最终确定组合抗病毒疗法的功效 非洲裔美国人的慢性HCV并定义宿主和病毒机制 这构成了治疗结果中种族差异的基础。因此，我们 建议巴尔的摩临床中心参加多中心临床 慢性HCV-1（ViRAHEP-C）抗病疗法的耐药性研究。这 该奖项的长期目标是确定有效的抗病毒 感染HCV-1的非裔美国人的治疗。这些项目有四个 具体目的：i）确定对48的持续病毒学反应速率 在非西班牙裔，非洲人中，抗病毒疗法的结合疗法课程 美国和非西班牙裔美国人白色慢性HCV-1患者； 2）确定 哪些宿主和病毒因素预测了对 非西班牙裔，非裔美国人和 非西班牙裔美国人慢性HCV-I患者； 3）确定模式 非裔美国人和高加索慢性的HCV（RNA）动力学。 HCV-1患者 在抗病毒治疗期间； 4）确定早期HCV（RNA）动力学是否 准确地预测治疗的终结和持续的病毒反应 抗病毒后，非裔美国人和高加索慢性HCV-I患者 治疗。与辅助研究合作，该项目将调查 选定病毒和宿主因素对治疗功效的影响 对于慢性HCV。这些研究可能为您提供重要的新见解 HCV的发病机理并导致慢性HCV的新疗法。