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: 8068356
• 负责人: MICHAEL W FRIED
• 金额: $ 16.26万
• 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/8068356
• 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）：慢性病毒肝炎是发病率和死亡率的主要原因。在过去的十年中，尽管这些疾病的管理策略不断发展，但在开发慢性丙型肝炎和丙型肝炎的新疗法方面发生了重大进展。在慢性丙型肝炎治疗的患者中，有一半以上的患者可以实现持续的病毒学反应。但是，由于医学或社会心理合并症，许多患者仍然无法实现永久性病毒，也不是初始抗病毒治疗的候选者，这是对Peginterferon和Ribavirin疗法的禁忌症。相反，作为核苷类似物的慢性丙型肝炎的治疗方法是更好的耐受性，尽管通常通过长期的病毒抑制来测量功效，而不是永久治愈。对于这两种疾病，更好地理解对治疗反应减少的机制，优化治疗方案的发展和/或鉴定替代或新型药物的鉴定至关重要。在迈克尔·弗里德（Michael Fried）博士的指导下，UNC肝脏疾病计划非常活跃，专注于治疗慢性病毒肝炎的研究。出于本应用的目的，我们将讨论由NCCAM/NIDDK资助的一项正在进行的I/II期研究，该研究研究了Silymarin（Milk Thistle）作为对未能对常规抗病毒药疗法反应反应的慢性肝炎患者（U01-AT003560，Synch）的替代治疗。此外，我们将回顾一项针对慢性肝炎B的新研究，乙型肝炎B临床研究网络，由NIDDK资助（U01 DK082867）。最后，我们将提出研究者发起的研究的详细概要，该研究利用新方法研究了外周血单核细胞中的干扰素信号传导途径。这些研究为初级教师和研究员提供了指导计划的骨干，他们积极参与其设计，实施和分析。正如本应用程序中所示的那样，受训者已经融入了这些研究活动中，这些研究活动为他们提供了在有指导环境中发展研究技能并主张其单个项目所有权的许多机会。 公共卫生相关性：在K24指导奖的竞争性续签申请中，我将提供有关我以患者为导向的研究背景以及成功的临床研究和综合指导计划的详细信息，该信息直接是由于该奖项而开发的。我还将展示我继续致力于临床研究，并向我担任主要导师的一群才华横溢的初级调查员。最后，我们将提供几项新的研究计划的例子，以确保有效的指导研究机会，以及制定能够进行转化研究研究的跨学科研究团队的计划。