Mentoring Junior Faculty: Viral hepatitis Clinical Research

指导初级教师：病毒性肝炎临床研究

• 批准号: 8262702
• 负责人: MICHAEL W FRIED
• 金额: $ 15.33万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8262702
• 关键词: 18 year old; Adherence; Adverse event; Alanine; Alternative Medicine; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Antiviral Agents; Antiviral Therapy; Apoptosis; Award; Biological Markers; Blood specimen; Chronic Hepatitis B; Chronic Hepatitis C; Chronic viral hepatitis; Clinical; Clinical Research; Clinical Trials; Comorbidity; Conduct Clinical Trials; Coupled; Data; Dedications; Development; Development Plans; Disease; Dose; Dose-Limiting; Drug Kinetics; Enrollment; Ensure; Environment; Evaluation; Faculty; Funding; Hepatic; Hepatitis B; Hepatitis C virus; Human; Immune response; Individual; Inflammation; Interdisciplinary Study; Interferons; Isomerism; Legalon; Liver diseases; Masks; Measures; Medical; Mentors; Methodology; Milk Thistle; Monitor; Morbidity - disease rate; National Center for Complementary and Alternative Medicine; National Institute of Diabetes and Digestive and Kidney Diseases; Normal Range; Outcome; Ownership; Oxidative Stress; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacodynamics; Phase; Placebos; Population; Preparation; RNA; Randomized; Research; Research Activity; Research Personnel; Research Support; Ribavirin; Safety; Screening procedure; Serum; Severities; Signal Pathway; Silymarin; Time; Toxic effect; Transferase; Translational Research; Treatment Protocols; United States National Institutes of Health; Vertebral column; Viral; Viral hepatitis; alternative treatment; design; diaries; dosage; fibrogenesis; improved; mortality; novel; nucleoside analog; patient oriented research; placebo controlled study; primary outcome; programs; psychosocial; public health relevance; research study; response; silibinin; silychristin; silydianin; skills; success; therapy development; treatment duration

DESCRIPTION (provided by applicant): Chronic viral hepatitis is a major global cause of morbidity and mortality. Over the last decade, significant progress has occurred in the development of new treatments for chronic hepatitis C and hepatitis B, although management strategy of these diseases continues to evolve. More than half of patients undergoing treatment with peginterferon and ribavirin for chronic hepatitis C can achieve a sustained virological response. However, numerous patients still fail to achieve permanent viral eradication or are not candidates for initial antiviral therapy due to medical or psychosocial comorbidities which are contraindications to peginterferon and ribavirin therapy. In contrast, treatments for chronic hepatitis B with nucleoside analogues, as examples, are better tolerated, although efficacy is generally measured by prolonged viral suppression, rather than permanent cure. For both these diseases, a better understanding of mechanisms of diminished response to therapy, development of optimized treatment regimens, and/or the identification of alternative or novel medications is of critical importance. The UNC Liver Diseases Program, under the direction of Dr. Michael Fried, is extremely active in pursuing studies that focus on treatment of chronic viral hepatitis. For the purposes of this application, we will discuss an ongoing phase I/II study, funded by NCCAM/NIDDK, that investigates silymarin (milk thistle) as an alternative treatment for patients with chronic hepatitis C who failed to respond to conventional antiviral therapy (U01-AT003560, SyNCH). Furthermore, we will review a new study for chronic hepatitis B, the Hepatitis B Clinical Research Network, funded by NIDDK (U01 DK082867). Finally, we will present a detailed synopsis of an investigator initiated study that examines interferon signaling pathways in peripheral blood mononuclear cells utilizing novel methodologies. These studies provide the backbone of the mentoring program for junior faculty and fellows who are actively involved in their design, implementation, and analysis. As demonstrated within this application, mentees have been integrated into these research activities which have provided them with numerous opportunities in a mentored environment within which to develop research skills and to assert their ownership of individual projects. PUBLIC HEALTH RELEVANCE: In this competing renewal application for the K24 Mentoring Award, I will provide detailed information regarding my background in patient-oriented research and the successful clinical research and integrated mentoring program that has been developed directly as a result of this award. I will also demonstrate my continued dedication to clinical research and to a diverse group of talented junior investigators for whom I serve as primary mentor. Finally, we will provide examples of several new research initiatives that will continue to ensure effective mentored research opportunities, as well as a plan for the development of interdisciplinary research teams capable of performing translational research studies.

描述（由申请人提供）：慢性病毒性肝炎是全球发病和死亡的主要原因。在过去的十年中，尽管慢性丙型肝炎和乙型肝炎的管理策略不断发展，但慢性丙型肝炎和乙型肝炎新疗法的开发取得了重大进展。超过一半接受聚乙二醇干扰素和利巴韦林治疗慢性丙型肝炎的患者可以获得持续的病毒学应答。然而，许多患者仍然未能实现永久病毒根除，或者由于医学或心理社会合并症而无法进行初始抗病毒治疗，而这些合并症是聚乙二醇干扰素和利巴韦林治疗的禁忌症。相比之下，用核苷类似物治疗慢性乙型肝炎的耐受性更好，尽管疗效通常是通过延长病毒抑制而不是永久治愈来衡量的。对于这两种疾病，更好地了解治疗反应减弱的机制、开发优化的治疗方案和/或识别替代或新型药物至关重要。北卡罗来纳大学肝脏疾病项目在迈克尔·弗里德博士的指导下，非常积极地致力于慢性病毒性肝炎治疗的研究。出于本申请的目的，我们将讨论一项由 NCCAM/NIDDK 资助的正在进行的 I/II 期研究，该研究研究水飞蓟素（水飞蓟）作为对传统抗病毒治疗无效的慢性丙型肝炎患者的替代治疗方法（U01-AT003560，SyNCH）。此外，我们将回顾一项由 NIDDK (U01 DK082867) 资助的慢性乙型肝炎新研究，即乙型肝炎临床研究网络。最后，我们将介绍一项研究人员发起的研究的详细概要，该研究利用新方法检查外周血单核细胞中的干扰素信号通路。这些研究为积极参与其设计、实施和分析的初级教师和研究员提供了指导计划的支柱。正如本申请中所展示的，受指导者已融入这些研究活动，这为他们在指导环境中提供了大量机会，在其中发展研究技能并维护他们对各个项目的所有权。 公共健康相关性：在 K24 指导奖的竞争续展申请中，我将提供有关我在以患者为导向的研究方面的背景以及因该奖项而直接开发的成功临床研究和综合指导计划的详细信息。我还将向我担任主要导师的一群才华横溢的初级研究人员展示我对临床研究的持续奉献精神。最后，我们将提供几项新的研究举措的例子，这些举措将继续确保有效的指导研究机会，以及发展能够进行转化研究的跨学科研究团队的计划。