Optimizing Measures for Clinical Trials in Covert Hepatic Encephalopathy

隐性肝性脑病临床试验的优化措施

• 批准号: 10132309
• 负责人: Elliot Tapper
• 金额: $ 19.4万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132309
• 关键词: Abdominal Muscles; Address; Adrenergic beta-Antagonists; Adverse event; Albumins; American; Ammonia; Area; Ascites; Bilirubin; Blood; Brain; Calibration; Calories; Catabolic Process; Cessation of life; Chronic; Cirrhosis; Clinical; Clinical Trials; Clinical Trials Design; Code; Coma; Complication; Computers; Confusion; Data; Data Analyses; Development; Diagnosis; Diet; Dietary Intervention; Disorientation; Electronic Mail; Enrollment; Executive Dysfunction; Exercise; Exposure to; Fall prevention; Feasibility Studies; Focus Groups; Goals; Gold; Grant; Hand; Hemorrhage; Hepatic Encephalopathy; Hospitalization; Inpatients; Intervention; Interview; Investigation; Knowledge; Lethargies; Malnutrition; Master' s Degree; Measures; Mentorship; Methodology; Methods; Modeling; Muscle; Muscle function; Nutritional; Online Systems; Outcome; Outpatients; Pathway interactions; Patient Outcomes Assessments; Patient Selection; Patients; Personal Satisfaction; Pharmaceutical Preparations; Physical Function; Portal Hypertension; Positioning Attribute; Prospective cohort; Proteins; Publishing; Randomized Controlled Trials; Research; Research Personnel; Retrospective cohort; Risk; Risk Factors; Severities; Structure; Talents; Testing; Text Messaging; Time; Training; Training Programs; Voice; Work; abdominal CT; arm; authority; base; career; chronic liver disease; clinical investigation; clinical predictors; cognitive change; cognitive function; cohort; cost; daily functioning; disability; executive function; exercise intervention; falls; grasp; health care service utilization; health related quality of life; high risk; improved; inattention; insight; modifiable risk; mortality; neurocognitive test; neuropsychiatry; novel; nutrition; patient oriented; point of care; predictive modeling; prevent; prospective; randomized trial; resistance exercise; response; risk prediction; risk stratification; sarcopenia; success; therapeutic target; therapy design; tool; vehicular accident; wasting

Optimizing Measures for Clinical Trials in Covert Hepatic Encephalopathy PI: Elliot B. Tapper, MD Among all complications of cirrhosis, none is more devastating than hepatic encephalopathy (HE). Although it will afflict up to 40% of patients with cirrhosis, HE has few dedicated researchers. A spectrum of neuropsychiatric disability, HE ranges in severity from covert (deficits in executive function) to overt (confusion, even coma). Even covert HE – the earliest stage – is independently associated with repeated hospitalization, falls, motor vehicle accidents and death. Unfortunately, strategies to prevent the development HE are limited. Furthermore, investigations of potential therapies are complicated by limited knowledge of both the clinical predictors of HE and impact on patient well-being and daily functions. This grant proposes to close these gaps. The training program aims to prepare the applicant for a career vested in identifying risk factors for HE, and in designing interventions to prevent HE and to improve patient well-being. A master's degree in clinical investigation with targeted additional courses will provide training in clinical trial design, calibration of patient reported measures for clinical trials, and longitudinal data analysis to develop clinical predictive models. The mentorship team assembled is diverse and talented, including Dr. Anna Lok (a clinical trialist and content expert), Dr. Jasmohan Bajaj (an authority on HE and clinical trials), Dr. Noelle Carlozzi (a neuropsychologist with expertise in mixed-methodology), and Dr. Susan Murphy (a trialist with a focus on interventions for frail patients). In research aim 1, we will determine the most important domains of health related quality of life (HRQOL) for patients with covert HE. In Aim 2, we will analyze a cohort of 300 cirrhosis patients without HE followed for up to 4 years to determine the modifiable risk factors for HE and to develop predictive models for HE and falls. In Aim 3, we will launch a pilot intervention aimed at the improvement of HRQOL and prevention of falls in patients with covert HE using a web-based platform that co-ordinates a combination of text-message, email and interactive-voice response to deliver structured encouragement to meet nutritional and exercise goals aimed at improving sarcopenia. By the conclusion of the K23, the applicant will be positioned for academic success with a niche in an important complication of cirrhosis and providing necessary preliminary data for an R01 supporting a larger, randomized trial.

优化隐匿性肝性脑病临床试验措施 PI：Elliot B.Tapper，医学博士 在肝硬变的所有并发症中，没有一种比肝性脑病(HE)更具破坏性。尽管它 将困扰高达40%的肝硬变患者，HE几乎没有专门的研究人员。一系列的 神经精神障碍，他的严重程度从隐蔽的(执行功能障碍)到显性的(精神错乱， 甚至昏迷)。即使是隐蔽的HE--最早的阶段--也独立地与反复住院有关， 跌倒、机动车事故和死亡。不幸的是，防止高等教育发展的战略是有限的。 此外，由于对两种临床治疗方法的了解有限，潜在治疗方法的研究也变得复杂起来。 肝性脑病的预测因子及其对患者幸福和日常功能的影响。这笔赠款建议弥合这些差距。 该培训计划旨在为申请者的职业生涯做好准备，包括确定HE的风险因素，以及 设计干预措施以预防HE并改善患者的福祉。临床硕士学位 具有针对性的附加课程的调查将提供临床试验设计、患者校准方面的培训 报告的临床试验措施，以及开发临床预测模型的纵向数据分析。这个 组建的导师团队是多样化和有才华的，包括安娜·洛克博士(临床试验和内容 专家)，Jasmohan Bajaj博士(HE和临床试验方面的权威)，Noelle Carlozzi博士(神经心理学家 在混合方法方面有专长)，以及苏珊·墨菲博士(专注于虚弱干预的三项试验 病人)。在研究目标1中，我们将确定与健康相关的生活质量的最重要的领域 (HRQOL)用于隐匿性HE患者。在目标2中，我们将分析300名未发生肝性脑病的肝硬变患者。 进行长达4年的跟踪调查，以确定HE的可修改风险因素，并开发预测模型 他摔倒了。在目标3中，我们将启动一项旨在改善HRQOL和预防的试点干预 使用基于网络的平台协调文本消息组合的隐匿性HE患者跌倒的概率， 电子邮件和交互式语音响应，提供结构化的鼓励，以满足营养和锻炼的要求 旨在改善石棺减少症的目标。到K23结束时，申请人将被定位为 在肝硬变的一个重要并发症中取得学术成功并提供必要的初步研究 支持更大规模随机试验的R01的数据。