Cognition in Clinical Trials for Huntington's Disease

描述（由申请人提供）：这份经修订的指导患者导向研究职业发展奖（K23）申请是为了资助Leigh J. Beglinger博士在亨廷顿病（HD）临床试验中认知结果评估方面的专业知识所必需的培训和研究活动。认知功能与许多重要因素高度相关，如疾病进展速度、工作能力、入住养老院前的时间长短、同意治疗和研究的能力以及患者和护理者的生活质量。然而，在大多数临床试验中，对认知的复杂评估却明显缺失。使用最佳可用工具设计和实施具有主要认知终点的临床试验的能力对于药物有效性和患者护理的完整评估至关重要。本申请中详细介绍的经过实质性修订的培训计划提供了一个多学科项目，利用爱荷华大学可用的各种资源和国家研究人员在神经精神病学临床试验方面的专业知识。作为一名神经心理学家，贝格林格博士现在寻求在临床试验设计、数据管理、复杂神经认知数据分析、多地点临床试验实施、伦理和拨款撰写方面的额外培训。本研究计划拟在36例成人轻度HD患者中开展一项试点临床试验，以实现以下研究目标：1)比较西酞普兰与安慰剂对早期HD患者执行功能和其他结局变量的影响，包括功能测量（健康相关的生活质量、工作效率和自我报告的注意力）、运动表现和精神状态。2)研究早期HD患者执行功能与功能状态之间的关系。培训和拟议的项目将为贝格林格博士的长期科学目标奠定基础，该目标是创建一个独立的研究项目，评估神经精神病学临床试验中的认知和功能结果。确定改善早期HD患者认知和精神症状的方法显然符合NINDS的使命，因为它可以提供有关减轻这种神经系统疾病对患者和家属负担的信息。

DESCRIPTION (provided by applicant): This revised Mentored Patient-Oriented Research Career Development Award (K23) application is a request for funding to support the training and research activities necessary for Leigh J. Beglinger, Ph.D. to develop expertise in the assessment of cognitive outcomes in Huntington's disease (HD) clinical trials. Cognitive functioning is highly related to many important factors such as rate of disease progression, ability to work, length of time before nursing home placement, capacity to consent to treatment and research, and quality of life for the patient and caregiver. Yet, the sophisticated assessment of cognition in most clinical trials is strikingly absent. The ability to design and implement clinical trials with primary cognitive endpoints using the best available tools will be critically important in the complete evaluation of drug effectiveness and patient care. The substantially revised training plan detailed in this application offers a multidisciplinary program capitalizing both on the diverse resources available at the University of Iowa and on the expertise of national researchers in neuropsychiatric clinical trials. As a neuropsychologist, Dr. Beglinger now seeks additional training in clinical trials design, data management, analysis of complex neurocognitive data, implementation of multi-site clinical trials, ethics and grantwriting. This research plan proposes to conduct a pilot clinical trial in 36 adults with mild HD to address the following research aims: 1) To determine the effect of citalopram compared to placebo in patients with early HD on executive function and other outcome variables including functional measures (health-related quality of life, work productivity, and self-reported attention), motor performance, and psychiatric status and 2) To study the relationship between executive function and functional status in patients with early HD. The training and proposed project will lay the foundation for Dr. Beglinger's long-term scientific goal of creating an independent program of research assessing cognitive and functional outcomes in neuropsychiatric clinical trials. Identifying means of improving cognitive and psychiatric symptoms in early HD clearly fits with the mission of NINDS, in that it could provide information about reducing the burden of this neurological disease to the patient and family.