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(丙型肝炎)是慢性肝病和 美国肝硬变，影响300万美国居民和 每年造成8-1万人死亡。每年因以下原因死亡的人数 预计到2010-2015年，慢性丙型肝炎病毒将增加两倍，因为个人在 感染发生率最高的是终末期肝硬变。丙型肝炎病毒 非裔美国人的感染率是白人的两倍 美国人。此外，非裔美国人的结果似乎更糟， 原发性肝细胞癌的发病率和死亡率较高 因肝硬变和肝细胞癌而导致的死亡率。很少有非洲裔美国人参加啤酒比赛 丙型肝炎病毒治疗的临床试验。然而，现有的数据显示， 干扰素治疗后长期丙型肝炎病毒转阴率较低 单独治疗和干扰素联合利巴韦林(RBV)与White的比较 美国人。在非裔美国人中，抗病毒治疗的疗效较低 部分原因是丙型肝炎病毒1型(丙型肝炎病毒-1)感染率较高。 然而，经丙型肝炎病毒基因型调整后的丙型肝炎病毒长期清除率仍然较低。 非洲裔美国人患者，暗示宿主可能扮演重要角色 决定较低治疗应答率的因素。有一个关键的问题 需要有足够数量的非裔美国人进行多中心临床试验 目的：明确联合抗病毒治疗的疗效。 非裔美国人慢性丙型肝炎病毒感染及其宿主和病毒机制的研究 这构成了治疗结果中的种族差异的基础。因此，我们 建议巴尔的摩临床中心参与多中心临床 慢性丙型肝炎病毒1型(VIRAHEP-C)对抗病毒治疗的耐药性研究这个 该奖项的长期目标是确定有效的抗病毒药物 非裔美国人感染丙型肝炎病毒的治疗(S)。这些项目有四个 具体目标：i)确定48岁以下儿童的持续病毒学应答率 在非西班牙裔非洲人中进行为期一周的联合抗病毒治疗 美国和非西班牙裔、美国白人慢性丙型肝炎病毒1型患者；2)确定 哪些宿主和病毒因子可预测对 非西班牙裔、非裔和非裔美国人的联合抗病毒治疗 非西班牙裔美国白人慢性丙型肝炎患者；3)确定模式 非裔美国人和高加索人慢性丙型肝炎病毒(RNA)动力学的研究。丙型肝炎病毒1型患者 在抗病毒治疗期间；4)确定早期丙型肝炎病毒(RNA)动力学 准确预测治疗结束和持续的病毒学应答 非洲裔美国人和高加索人慢性丙型肝炎患者服用抗病毒药物 心理治疗。在辅助研究的协作下，该项目将调查 选择的病毒和宿主因素对治疗效果的影响 治疗慢性丙型肝炎病毒。这些研究可能会为我们提供关于 丙型肝炎病毒的发病机制，并导致慢性丙型肝炎的新疗法。