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.

项目概要 过去十年，青少年自杀率急剧上升，目前自杀已成为第二大自杀事件。 15-24 岁人群死亡的主要原因。没有有效的治疗方法可以降低风险 青少年的自杀行为，目前可用的标准治疗效果有限，并且通常需要 几周或几个月才能生效。因此，迫切需要找到快速起效的治疗方法 改善与自杀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方面的功效，以及一项开放标签研究 对于青少年来说，氯胺酮似乎是治疗最近发生自杀事件的青少年的一种有前景的方法。 我们建议对近期有自杀行为的青少年进行首次氯胺酮随机对照试验。 所有青少年都将在针对有自杀倾向的青少年的强化门诊项目中接受治疗，并将 随机接受静脉注射氯胺酮 0.5mg/kg 或咪达唑仑 0.02mg/kg，两周内输注四次 开始 IOP 后 +/- 十天内。我们还将使用死亡/自杀来检查隐性认知关联 内隐联想测试（IAT）。所有参与者将被跟踪 12 周以评估：1）重复次数的减少 12 周内自杀企图，2) 2 周研究治疗内隐性自杀认知减少 3）在两周的研究期内抑郁症和自杀意念的减少。我们还将 探讨 IAT 的减少是否会在 12 周内介导自杀倾向的改善。迄今为止，还没有研究 报告了以下证据：1) 使用氯胺酮可减少成人或青少年的重复自杀事件（AIM 1）， 2) 青少年内隐认知（AIM 2）或与自杀相关的症状（AIM 3）减少， 3）介导（AIM 4）氯胺酮对自杀影响的潜在机制。创新功能 包括：1) 它针对的是高危青少年中在高危时期重复自杀事件的人，这些青少年通常是 被排除在临床试验之外； 2) 是跨诊断的； 3）无缝集成当前护理标准；和 4) 评估可以在临床需求最大的时间和地点提供的干预措施，但对于 目前还没有制定干预措施。