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.

隐匿性肝性脑病临床试验的优化措施 PI：Elliot B.马里兰州塔珀 在肝硬化的所有并发症中，没有一种比肝性脑病（HE）更具破坏性。虽然 将折磨高达40%的肝硬化患者，HE几乎没有专门的研究人员。的光谱 神经精神残疾，HE的严重程度从隐性（执行功能缺陷）到显性（混乱， 甚至昏迷）。即使是隐性HE -最早期-也与反复住院独立相关， 福尔斯、机动车事故和死亡。不幸的是，防止HE发展的策略是有限的。 此外，对潜在疗法的研究由于对临床和病理学的知识有限而变得复杂。 HE的预测因素以及对患者健康和日常功能的影响。这笔赠款旨在弥补这些差距。 该培训计划旨在为申请人的职业生涯做好准备，以确定HE的风险因素， 设计干预措施以预防HE并改善患者健康。临床医学硕士学位 有针对性的额外课程的调查将提供临床试验设计，患者校准 报告临床试验的措施和纵向数据分析，以开发临床预测模型。的 导师团队成员多元化，才华横溢，包括安娜洛克博士（临床试验和内容 专家），Jasmohan Bajaj博士（HE和临床试验的权威），Noelle Carlozzi博士（神经心理学家 具有混合方法学方面的专业知识）和Susan Murphy博士（一位专注于脆弱人群干预的试验者） 患者）。在研究目标1中，我们将确定健康相关生活质量的最重要领域 （HRQOL），用于隐性HE患者。在目标2中，我们将分析300名无HE的肝硬化患者队列 随访长达4年，以确定HE的可改变风险因素，并建立预测模型， 他和福尔斯。在目的3方面，我们会推行一项先导计划，以改善健康相关生活质量和预防 的福尔斯在隐性肝性脑病患者使用基于网络的平台， 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 目的是改善肌肉减少症。到K23结束时，申请人将定位于 学术上的成功与一个小生境的重要并发症肝硬化，并提供必要的初步 R 01的数据支持更大的随机试验。