Double-Blind Randomized Controlled Trial of Acute-Course of Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents

氯胺酮与咪达唑仑治疗青少年自杀复发急性病程的双盲随机对照试验

• 批准号: 10471358
• 负责人: MADHUKAR H. TRIVEDI
• 金额: $ 65.57万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10471358
• 关键词: Accident and Emergency department; Acute; Adolescent; Adult; Age; Age-Years; Caregivers; Caring; Cause of Death; Clinical; Clinical Trials; Cognition; Cognitive; Development; Double-Blind Method; Emergency department visit; Event; Family; Feeling suicidal; Female; Goals; Grant; Hospitalization; Hour; Implicit Association Test; Individual; Infusion procedures; Inpatients; Intervention; Interview; Intravenous; Ketamine; Knowledge; Length of Stay; Link; Measures; Mediating; Mediation; Medical; Medicine; Mental Depression; Midazolam; Participant; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Pharmacotherapy; Placebos; Provider; Psychotherapy; Randomized; Randomized Controlled Trials; Recurrence; Reporting; Research; Risk; Suicide; Suicide attempt; Testing; Time; Visit; Youth; aged; associated symptom; base; care seeking; clinical care; depressive symptoms; effectiveness trial; efficacy evaluation; enantiomer; experience; experimental study; high risk; innovation; male; novel therapeutics; open label; outpatient programs; prevent; programs; recruit; reduce symptoms; standard care; standard of care; suicidal; suicidal adolescent; suicidal behavior; suicidal morbidity; suicidal risk; suicide rate; symptomatic improvement; treatment duration

PROJECT SUMMARY Rates of suicide have increased dramatically in youths over the past decade, and suicide is now the 2nd leading cause of death for individuals ages 15-24. There are no validated treatments to decrease the risk of adolescent suicidal behavior, and currently available standard treatments are of modest benefit and often take weeks or months to become effective. Hence, there is an urgent need to identify rapid-acting treatments that ameliorate symptoms associated with suicidality and prevent repeat suicidal events. Based on evidence for efficacy of ketamine in reducing symptoms of suicidality in adults, as well as an open label study in adolescents, ketamine appears to be a promising treatment approach for youths with a recent suicidal event. We propose to conduct the first randomized, controlled trial of ketamine in youth with recent suicidal behaviors. All youth will be in treatment in an intensive outpatient program for suicidal adolescents, and will be randomized to intravenous ketamine 0.5mg/kg or midazolam 0.02mg/kg for four infusions over two weeks within +/- ten days of starting IOP. We will also examine implicit cognitive associations using the Death/Suicide Implicit Association Test (IAT). All participants will be followed for 12 weeks to evaluate: 1) reduction in repeat suicide attempts over 12 weeks, 2) reduction in implicit suicidal cognition within the 2-week study treatment period, and 3) reduction in depression and suicidal ideation within the 2-week study period. We will also explore whether reductions in IAT mediates improvement in suicidality over 12 weeks. To date, no study has reported evidence for 1) reduction in repeat suicidal events with ketamine either in adults or in youths (AIM 1), 2) reductions either in implicit cognition (AIM 2) or in symptoms associated with suicidality (AIM 3) in youths, and 3) underlying mechanisms that mediate (AIM 4) the effects of ketamine on suicidality. Innovative features include: 1) it targets repeat suicidal events during a high-risk period in high-risk youths who are typically excluded from clinical trials; 2) is transdiagnostic; 3) seamlessly integrates in current standard of care; and 4) evaluates an intervention that can be delivered at a time and place when there is greatest clinical need, but for which there are no currently developed interventions.

项目摘要 在过去的十年中，年轻人的自杀率急剧上升，自杀现在是第二名 15-24岁的个体的主要死亡原因。没有经过验证的治疗方法来降低 青春期的自杀行为，目前可用的标准治疗是适度的好处，经常采取 几周或几个月才能有效。因此，迫切需要识别快速行动的治疗 改善与自杀性相关的症状并防止重复自杀事件。基于证据 氯胺酮在减少成人自杀症状的功效，以及一项开放标签研究 青少年，氯胺酮似乎是最近一次自杀事件的年轻人的一种有前途的治疗方法。 我们建议在最近具有自杀行为的青年中进行氯胺酮的第一个随机对照试验。 所有年轻人都将在一项针对自杀青少年的强化门诊病人计划中接受治疗，并将 在两周内随机分配至静脉注射氯胺酮0.5mg/kg或咪达唑仑402mg/kg 在启动IOP的+/-十天之内。我们还将使用死亡/自杀来检查隐性认知关联 隐式协会测试（IAT）。所有参与者将被遵循12周的评估：1）重复减少 在12周内的自杀企图，2）在2周的研究治疗中降低了隐式自杀认知 周期和3）在为期2周的研究期内抑郁症和自杀念头的减少。我们也会 探索IAT的减少是否介导了12周内自杀性的改善。迄今为止，没有研究 报告有证据表明1）在成年人或年轻人中，氯胺酮重复自杀事件减少（AIM 1）， 2）减少隐式认知（目标2）或与自杀性相关的症状（AIM 3）中的减少（AIM 3） 3）介导（目标4）氯胺酮对自杀性的影响的基本机制。创新功能 包括：1）它针对高危年轻人的高风险时期重复自杀事件的目标 排除在临床试验之外； 2）是经诊断的； 3）无缝集成到当前的护理标准中；和4） 评估一种干预措施，可以在有最大临床需求时在一次和地点进行的干预措施，但 目前没有开发干预措施。