Optimizing Measures for Clinical Trials in Covert Hepatic Encephalopathy

隐性肝性脑病临床试验的优化措施

基本信息

批准号：
10382474
负责人：
Elliot Tapper
金额：
$ 19.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/10382474
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&apos 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

项目摘要

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.

隐性肝性脑病临床试验的优化措施 PI：Elliot B. Tapper，医学博士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。高达 40% 的肝硬化患者会受到这种疾病的困扰，但 HE 的专门研究人员却很少。神经精神障碍，HE 的严重程度从隐性（执行功能缺陷）到显性（意识混乱、即使是隐性 HE（最早阶段）也与反复住院独立相关，不幸的是，预防 HE 发展的策略是有限的。此外，由于对临床和治疗的了解有限，对潜在疗法的研究变得复杂。 HE 的预测因素以及对患者健康和日常功能的影响。这项拨款旨在弥补这些差距。该培训计划旨在帮助申请人为从事识别高等教育风险因素的职业做好准备，并在设计预防 HE 和改善患者健康的干预措施。具有针对性的额外课程调查将提供临床试验设计、患者校准方面的培训报告了临床试验的措施，以及开发临床预测模型的纵向数据分析。导师团队多元化且才华横溢，其中包括 Anna Lok 博士（临床试验师和内容专家）、Jasmohan Bajaj 博士（HE 和临床试验权威）、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（一位专注于对虚弱者进行干预的试验者）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领域。隐性 HE 患者的 HRQOL（HRQOL）在目标 2 中，我们将分析 300 名无 HE 的肝硬化患者。随访长达 4 年以确定 HE 的可改变风险因素并开发预测模型 HE 和跌倒在目标 3 中，我们将启动一项旨在改善 HRQOL 和预防的试点干预措施。使用基于网络的平台协调短信组合，减少隐性 HE 患者跌倒的情况，电子邮件和交互式语音回复提供结构化的鼓励，以满足营养和锻炼的要求旨在改善肌肉减少症的目标在 K23 结束时，申请人将定位于：学术上的成功，在肝硬化的重要并发症中占有一席之地，并提供必要的初步准备 R01 的数据支持更大规模的随机试验。