Pimavanserin for Insomnia in Veterans with Post-traumatic Stress Disorder

匹马范色林治疗患有创伤后应激障碍的退伍军人的失眠

• 批准号: 10480269
• 负责人: Melissa Beth Jones
• 金额: --
• 依托单位: MICHAEL E DEBAKEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10480269
• 关键词: Address; Adult; Adverse event; Aftercare; Agonist; Applications Grants; Award; Benzodiazepines; Biometry; Book Chapters; Cementation; Chicago; Chronic Insomnia; Chronic Post Traumatic Stress Disorder; Clinical; Clinical Trials; Clinical Trials Design; Cognitive Therapy; Country; DSM-V; Delusions; Double-Blind Method; Dropout; Drowsiness; Education; Effectiveness; Enrollment; Environment; Faculty; Fellowship; Female; Funding; Future; GABA Agonists; Goals; HTR2A gene; Hallucinations; Health; Health Services Research; Illinois; Instruction; Intervention; Manuscripts; Measures; Medical center; Medicine; Mental Health Services; Mental disorders; Mentors; Mentorship; Neurodegenerative Disorders; Outcome Measure; Parkinson Disease; Patients; Peer Review; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Placebo Control; Placebos; Polysomnography; Post-Traumatic Stress Disorders; Protocols documentation; Psychiatrist; Psychiatry; Psychopathology; Psychoses; Psychotherapy; Publishing; Randomized; Refractory; Reporting; Research; Residencies; Resistance; Risk; Safety; Sampling; Scientist; Severities; Sleep; Sleep Architecture; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Stage I Sleep; Stress; Symptoms; Time; Training; Trazodone; United States Food and Drug Administration; Universities; Veterans; actigraphy; addiction liability; atypical antipsychotic; behavioral neurology; career; career development; clinical center; college; design; effective intervention; efficacy clinical trial; efficacy evaluation; evidence base; falls; hangover; healthy volunteer; improved; improvement on sleep; indexing; innovation; male; medical schools; meetings; memory consolidation; memory process; neuropsychiatry; novel; placebo group; post-traumatic symptoms; primary outcome; professor; randomized, clinical trials; screening; side effect; sleep onset; sleep quality; statistics; suicidal risk; supplemental instruction

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.

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了学业。 医学，芝加哥伊利诺伊大学精神病学住院医师， 贝勒医学院的行为神经学和神经精神病学，以及一项研究 中南精神疾病研究、教育和临床中心奖学金 （MIRECC）在Michael E. DeBakey VA医疗中心（MEDVAMC）。她目前是 精神卫生保健线在MEDVAMC和助理教授精神科医生 精神科在芝加哥。她发表了6篇第一作者和2篇合著的同行评审论文。 手稿和1第一作者的书章。琼斯博士渴望成为一名独立的 临床科学家设计和执行新的睡眠干预临床试验， 创伤性应激障碍（PTSD）和其他影响美国退伍军人的神经精神疾病。 她最终的目标是利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：在此期间，博士。 Jones将获得临床试验设计和执行、生物统计学以及 研究评估失眠和创伤后应激障碍需要她实现研究 独立作为一个干预治疗这些和其他流行的神经精神 干扰.这项培训是通过与她的导师团队举行正式会议来完成的 统计学和药理学的课程，以及睡眠医学的补充指导。 环境：MEDVAMC和创新质量、有效性和安全中心 （IQuEST）提供理想的研究和培训环境，以完成拟议的 项目MEDVAMC为世界上最多的独特退伍军人提供心理健康护理。 国家IQuEST是西南地区卫生服务研究的首要中心。 研究：迫切需要采取有效的干预措施，以解决普遍存在的 与创伤后应激障碍有关的顽固性失眠几条证据表明匹莫范色林， 5-HT 2A反向激动剂，可能有益于PTSD相关的睡眠障碍。因此，目标1是 对匹莫范色林34 mg的疗效进行初步随机临床试验（RCT） 在睡前给药8周，用于治疗患有创伤后应激障碍的退伍军人的失眠。48 患有慢性失眠症和PTSD的成年男性和女性退伍军人被随机分配到 睡前接受匹莫范色林34 mg或安慰剂8周;失眠的平均变化 在治疗前和治疗后比较各组之间的严重程度。虽然目标1考察主观 目标2描述了多导睡眠描记术的睡眠客观测量， 治疗前和治疗后的活动记录仪。目的3（探索性）检查匹莫范色林34 mg 在美国退伍军人中，连续8周的睡前睡眠可以降低与压力相关的精神病理学的严重程度 与安慰剂组相比有显著性差异。该试点RCT介绍了可行性， 我们方案的耐受性和匹莫范色林对睡眠结构的潜在影响。最后， 该提案为未来的赠款提案提供了框架，以进行更大的，充分的 有把握的RCT旨在检测以下患者失眠严重程度的有意义的临床差异： pimavanserin治疗。