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: 10264146
• 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/10264146
• 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 在过去的十年里，年轻人的自杀率急剧上升，自杀现在是第二大自杀。 是15-24岁人群的主要死因没有有效的治疗方法来降低 青少年自杀行为，目前可用的标准治疗是适度的好处，往往采取 几周或几个月才能生效。因此，迫切需要确定速效治疗方法， 改善与自杀倾向相关的症状并预防重复自杀事件。根据证据， 氯胺酮在减轻成人自杀症状方面的疗效，以及一项在 对于青少年来说，氯胺酮似乎是最近有自杀事件的青少年的一种有希望的治疗方法。 我们建议在近期有自杀行为的年轻人中进行第一次氯胺酮的随机对照试验。 所有的青少年都将在一个针对自杀青少年的强化门诊项目中接受治疗， 随机分配至静脉注射氯胺酮0.5mg/kg或咪达唑仑0.02mg/kg，在两周内输注4次 在开始IOP的+/-10天内。我们还将使用死亡/自杀来检查内隐认知关联 内隐联想测验（IAT）。所有参与者将被随访12周，以评估：1）减少重复 12周内的自杀企图，2）2周研究治疗内的内隐自杀认知减少 3）在2周的研究期内抑郁和自杀意念的减少。我们还将 探索IAT的降低是否介导了12周内自杀倾向的改善。到目前为止，没有任何研究 报告的证据表明：1）氯胺酮在成人或青年中的重复自杀事件减少（AIM 1）， 2)内隐认知（AIM 2）或与青年自杀相关的症状（AIM 3）减少， （3）介导（AIM 4）氯胺酮对自杀行为影响的潜在机制。创新特色 包括：1）它针对高危青少年在高危时期重复自杀事件，这些青少年通常 从临床试验中排除; 2）是跨诊断的; 3）无缝集成在当前的护理标准中;以及4） 评估可以在临床需求最大的时间和地点进行的干预，但 目前还没有开发出干预措施。