Pimavanserin for Insomnia in Veterans with Post-traumatic Stress Disorder

候选人：梅丽莎·贝丝·琼斯博士在德雷克塞尔大学医学院完成学业 医学，芝加哥伊利诺伊大学精神病学住院医师，临床研究员 贝勒医学院的行为神经学和神经精神病学，以及一项研究 中南部精神疾病、研究、教育和临床中心联谊会 (MIRECC)，Michael E.DeBakey VA医疗中心(MEDVAMC)。她目前是一名 精神卫生保健部门的精神病学家，助理教授 BCM的精神病学。她发表了6篇第一作者和2篇合著的同行评议文章 手稿和一本书的第一章。琼斯博士渴望成为一名独立的 临床医生-科学家设计和执行新的睡眠干预措施的临床试验， 创伤应激障碍(PTSD)和其他影响美国退伍军人的神经精神疾病。 她最终的目标是使用这些干预措施来改变风险或出现 神经退行性疾病。职业发展和目标：在此获奖期间，Dr。 琼斯将在临床试验设计和执行、生物统计学和 她完成研究所需的失眠和创伤后应激障碍的研究评估 作为一名干预者，独立治疗这些和其他流行的神经精神疾病 骚乱。这项培训是通过与她的正式指导团队举行会议来完成的 统计学和药理学的课程作业，以及睡眠医学的补充指导。 环境：MEDVAMC和创新质量、效率和安全中心 (Quest)提供理想的研究和培训环境，以完成拟议的 项目。MEDVAMC为世界上最多的独一无二的退伍军人提供心理健康护理 国家。Quest是西南地区首屈一指的卫生服务研究中心。 研究：迫切需要有效的干预措施来解决普遍存在的 与创伤后应激障碍相关的顽固性失眠。几行证据表明，吡喃西林， 5-HT2A反向激动剂，可能有益于创伤后应激障碍相关的睡眠障碍。因此，目标1是 对吡喃色林34 mg的疗效进行初步随机临床试验 睡前给药8周，用于治疗患有创伤后应激障碍的退伍军人失眠。48 患有慢性失眠障碍和创伤后应激障碍的成年男性和女性退伍军人被随机分为 睡前服用匹马西林34毫克或安慰剂8周；平均失眠改变 比较两组治疗前后的严重程度。而目标1则考察主观性 睡眠测量，目标2用多导睡眠图和睡眠图来表征客观的睡眠测量 治疗前后的肌动描记。目标3(探索性)检查匹马昔林34 mg 睡前8周可降低美国退伍军人应激相关精神病的严重程度 与安慰剂相比，创伤后应激障碍和失眠。这项试点RCT通知了可行性和 我们的方案的耐受性以及吡喃色林对睡眠结构的潜在影响。最终， 该提案为未来的赠款提案提供了框架，以执行更大、更充分的 动力式随机对照试验旨在检测以下失眠严重程度的有意义的临床差异 用匹马西林治疗。

Candidate: Dr. Melissa Beth Jones completed medical school at Drexel University College of Medicine, psychiatry residency at University of Illinois at Chicago, clinical fellowship in Behavioral Neurology & Neuropsychiatry at Baylor College of Medicine (BCM), and a research fellowship in the South Central Mental Illness, Research, Education and Clinical Center (MIRECC) at the Michael E. DeBakey VA Medical Center (MEDVAMC). She is currently a faculty psychiatrist in the Mental Health Care Line at MEDVAMC and Assistant Professor of Psychiatry at BCM. She has published 6 first-authored and 2 co-authored peer-reviewed manuscripts and 1 first-authored book chapter. Dr. Jones aspires to become an independent clinician-scientist designing and executing clinical trials of novel interventions for sleep, post- traumatic stress disorder (PTSD), and other neuropsychiatric conditions impacting US Veterans. She eventually aims to use these interventions to modify the risk or emergence of neurodegenerative disorders. Career Development and Goals: During this award period, Dr. Jones will obtain the necessary training in clinical trial design and execution, biostatistics, and research assessments of insomnia and PTSD required for her to achieve research independence as an interventionalist treating these and other prevalent neuropsychiatric disturbances. This training is accomplished through meetings with her mentorship team, formal coursework in statistics and pharmacology, and supplemental instruction in sleep medicine. Environment: The MEDVAMC and Center for Innovation Quality, Effectiveness and Safety (IQuEST) provide the ideal research and training environments to complete the proposed project. MEDVAMC provides mental health care to the largest number of unique Veterans in the country. IQuEST is the premiere center for health services research in the southwest region. Research: There is a critical need for effective interventions to address the prevalent and refractory insomnia associated with PTSD. Several lines of evidence suggest that pimavanserin, a 5-HT2A inverse agonist, may benefit PTSD-related sleep disturbances. Accordingly, Aim 1 is to conduct a preliminary randomized clinical trial (RCT) of the efficacy of pimavanserin 34mg administered at bedtime for 8 weeks for the treatment of insomnia in Veterans with PTSD. 48 adult male and female Veterans with chronic insomnia disorder and PTSD are randomized to receive either pimavanserin 34mg or placebo at bedtime for 8 weeks; mean change in insomnia severity is compared between groups pre- and post-treatment. While Aim 1 examines subjective measures of sleep, Aim 2 characterizes objective measures of sleep with polysomnography and actigraphy pre- and post-treatment. Aim 3 (exploratory) examines whether pimavanserin 34mg at bedtime for 8 weeks reduces the severity of stress-related psychopathology in US Veterans with PTSD and insomnia compared to placebo. This pilot RCT informs on the feasibility and tolerability of our protocol and pimavanserin’s potential impact on sleep architecture. Ultimately, this proposal provides the framework for a future grant proposal to perform a larger, adequately powered RCT designed to detect a meaningful clinical difference in insomnia severity following treatment with pimavanserin.