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.
