EVALUATION OF THE EFFICACY OF THE NK1 ANTAGONIST GR205171 IN PTSD

NK1 拮抗剂 GR205171 在 PTSD 中的疗效评估

• 批准号: 7953677
• 负责人: Dennis S. Charney
• 金额: $ 2.08万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953677
• 关键词: Anxiety Disorders; Biological; Chronic; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Controlled Clinical Trials; Disease; Etiology; Event; Exposure to; Family; Functional disorder; Funding; Grant; Institution; Mental disorders; Neurologic; Neuropeptides; Neurosecretory Systems; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Placebo Control; Placebos; Post-Traumatic Stress Disorders; Preparation; Randomized; Research; Research Personnel; Resources; Selective Serotonin Reuptake Inhibitor; Societies; Source; Substance P; Suicide attempt; Surrogate Markers; System; Tachykinin; Therapeutic; United States National Institutes of Health; clinical remission; efficacy evaluation; improved; meetings; neuroimaging; novel; preclinical study; receptor; response; treatment response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Post-traumatic stress disorder (PTSD) is a chronic and common anxiety disorder that follows exposure to an overwhelming traumatic event. The majority of patients with PTSD also meet criteria for other psychiatric disorders and many attempt suicide. Despite its impact on society, little is known about the etiology or pathophysiology of this disorder. PTSD is responsive to pharmacological treatments such as selective serotonin reuptake inhibitors (SSRIs), but response rates rarely exceed 60%, and even fewer patients (20-30%) achieve clinical remission. Thus, there is a clear need to develop novel and improved therapeutics for PTSD. A growing body of preclinical studies suggests that activation of substance P (SP) and its NK1 receptor is anxiogenic and that NK1 antagonists, with chronic administration, exert significant dampening effects on this system. SP is a neuropeptide belonging to the tachykinin family, and has been implicated in several neurological and psychiatric illnesses. Excess activity of the SP-NK1 system thus stands as a prime candidate for involvement in the pathophysiology of anxiety disorders such as PTSD. We propose to investigate the efficacy of the highly specific NK1 antagonist GW597599 in PTSD in a placebo-controlled clinical trial. Furthermore, we propose to longitudinally investigate whether certain biological surrogate markers (neuroendocrine, neuroimaging) are predictive of treatment response. If a patient is already taking medication for PTSD and has achieved therapeutic response, he/she will not be tapered off effective medication(s) to participate in this study, and will not be eligible for the study. Taper and discontinuation of medications in preparation for this study will only occur in those patients who are not responding to medication treatment for PTSD. Hypotheses: 1)PTSD patients randomized to the NK1 antagonist GW597599 will achieve higher response rates acutely compared to patients randomized to placebo. 2)Biological surrogate makers involving neuroendocrine (CSF SP and NE) and neuroimaging function will be predictive of treatment response.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 创伤后应激障碍 (PTSD) 是一种慢性常见的焦虑症，发生于遭受压倒性的创伤事件后。 大多数患有创伤后应激障碍的患者也符合其他精神疾病的标准，并且许多人试图自杀。尽管它对社会产生影响，但人们对这种疾病的病因或病理生理学知之甚少。 PTSD 对选择性血清素再摄取抑制剂 (SSRI) 等药物治疗有反应，但缓解率很少超过 60%，达到临床缓解的患者更少 (20-30%)。 因此，显然需要开发针对 PTSD 的新颖且改进的疗法。 越来越多的临床前研究表明，P 物质 (SP) 及其 NK1 受体的激活具有致焦虑作用，并且长期服用 NK1 拮抗剂会对该系统产生显着的抑制作用。 SP 是一种属于速激肽家族的神经肽，与多种神经和精神疾病有关。因此，SP-NK1 系统的过度活性是参与 PTSD 等焦虑症病理生理学的主要候选者。 我们建议在一项安慰剂对照临床试验中研究高度特异性 NK1 拮抗剂 GW597599 对 PTSD 的疗效。 此外，我们建议纵向研究某些生物替代标志物（神经内分泌、神经影像）是否可以预测治疗反应。 如果患者已经在服用治疗 PTSD 的药物并取得了治疗反应，他/她将不会因参加本研究而逐渐减少有效药物的用量，也没有资格参加本研究。为了准备本研究而逐渐减少和停止药物治疗只会发生在那些对 PTSD 药物治疗没有反应的患者中。 假设： 1) 与随机接受安慰剂的患者相比，随机接受 NK1 拮抗剂 GW597599 治疗的 PTSD 患者将获得更高的急性缓解率。 2）涉及神经内分泌（CSF SP和NE）和神经影像功能的生物替代指标将预测治疗反应。