Glutamatergic Modulation to Facilitate Naltrexone Initiation: A Randomized, Controlled Trial

谷氨酸能调节促进纳曲酮启动：一项随机对照试验

• 批准号: 9309444
• 负责人: Elias Dakwar
• 金额: $ 62.09万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309444
• 关键词: Absence of pain sensation; Abstinence; Address; Admission activity; Affinity; Agonist; Anesthetics; Animal Experimentation; Antidepressive Agents; Anxiety; Buprenorphine; Characteristics; Clinic; Clinical; Conscious Sedation; Data; Development; Disease Management; Dose; Dropout; Drug Metabolic Detoxication; Epidemic; Formulation; Glutamates; Hospitals; Hour; Improve Access; Incidence; Individual; Infusion procedures; Injectable; Injection of therapeutic agent; Inpatients; Investigation; Ketamine; Maintenance; Mediator of activation protein; Methadone; Methods; Midazolam; Modeling; Moods; Morphine; Motivation; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Naltrexone; Opiate Addiction; Opioid; Oral; Overdose; Pain; Participant; Patients; Pattern; Pharmaceutical Preparations; Pharmacotherapy; Procedures; Protocols documentation; Randomized; Randomized Controlled Trials; Recurrence; Regimen; Relapse; Research; Research Personnel; Role; Schedule; Series; Severities; Substance Use Disorder; Time; Titrations; Withdrawal; active control; base; craving; disorder later incidence prevention; effective therapy; experience; improved; improved outcome; novel; opioid use; opioid use disorder; overdose death; pre-clinical; prevent; primary outcome; secondary outcome; treatment strategy

Project Summary The incidence of opioid use disorders (OUDs) has increased to near-epidemic proportions. Clinical researchers have a clear responsibility to improve access to long-term treatment in order to avoid the pattern of relapse, recurrent detoxification admissions, or overdose characteristic of present treatment efforts. While agonist maintenance with methadone or buprenorphine represents an effective long-term treatment strategy, it may be unacceptable to many individuals; this may compromise treatment seeking or prevent the initiation of maintenance treatment following detoxification. Long-acting injectable naltrexone (XR-NTX) robustly blocks the effects of opioids for at least 4 weeks and is now indicated for relapse prevention following detoxification. XR-NTX therefore represents an effective alternative to agonist treatment, but it is significantly underutilized due to hurdles associated with rapidly and tolerably transitioning active users. Indeed, about half of individuals fail to initiate XR-NTX in existing naltrexone titration protocols. Our data suggest that the N-methyl-D-aspartate receptor antagonist ketamine may be feasibly integrated into a 3-day rapid non-opioid based naltrexone titration, with sub-anesthetic infusions exerting apparent effects on spontaneous and precipitated withdrawal as well as on retention. In the proposed investigation, we aim to evaluate whether two 90-minute sub-anesthetic ketamine infusions (1.41 mg/kg), compared to 2 infusions of the control midazolam (0.04 mg/kg), improve outcomes in opioid dependent individuals engaged in a rapid non-opioid based oral naltrexone titration, followed by XR-NTX maintenance. The primary outcome will be the proportion of participants to initiate XR-NTX. Secondary outcomes include abstinence rates, 3-month retention, and withdrawal severity. The investigators' extensive experience with sub-anesthetic ketamine infusions and with antagonist-based treatment of opioid dependence supports the feasibility of this novel protocol. If successful, this trial would represent a major advance in efforts to identify novel pharmacotherapies for OUD management, and for addressing a critical hurdle in XR-NTX utilization. Thus it may pave the way for research into analogous compounds, such as ketamine- like antidepressants currently in development. This may ultimately serve to broaden access to effective maintenance treatment options for active users, and to reposition detoxification as a stepping-stone to long-term treatment. These data may therefore advance treatment efforts for OUDs and increase access to a larger repertoire of first-line treatments.

项目摘要 阿片类药物使用障碍（OUD）的发生率已增加到近乎流动的比例。 临床研究人员有明确的责任，以改善长期治疗的途径 为了避免复发模式，复发排毒入院或过量的特征 目前的治疗工作。而用美沙酮或丁丙诺啡维护激动剂 代表了一种有效的长期治疗策略，对于许多人来说可能是不可接受的。 这可能会损害寻求或阻止维护治疗的治疗 解毒后。长效注射纳曲酮（xr-ntx）稳健地阻止 阿片类药物至少4周，现在被指示用于排毒后的预防复发。 因此，XR-NTX代表了激动剂治疗的有效替代方法 由于与迅速和可忍受的过渡活跃用户相关的障碍而被充分利用。 实际上，大约一半的个体无法在现有Naltrexone滴定协议中启动XR-NTX。 我们的数据表明，N-甲基-D-天冬氨酸受体拮抗剂氯胺酮可能是可行的 集成为3天的快速非阿片类药物基于纳曲酮的滴定，并带有亚麻省输注 对自发性和沉淀的戒断以及保留产生明显的影响。在 拟议的调查，我们旨在评估两个90分钟的亚手提感觉氯胺酮是否 输注（1.41 mg/kg），而对照咪达唑仑（0.04 mg/kg）进行了2次输注 阿片类药物依赖性的个体的结果，从事快速非阿片类药物的口服纳曲酮 滴定，然后进行XR-NTX维护。主要结果将是 参与者启动XR-NTX。次要结果包括节制率，3个月保留率， 和撤回严重程度。调查人员在亚手提措施中的丰富经验 输注和基于拮抗剂的阿片类药物依赖治疗支持了这种可行性 新协议。如果成功，该审判将代表确定新颖的努力的重大进步 OUD管理的药物治疗，并解决XR-NTX中的关键障碍 利用率。因此，它可能为研究类似化合物的研究铺平了道路，例如氯胺酮 - 就像目前正在开发的抗抑郁药一样。这最终可能有助于扩大访问权限 为活跃用户提供有效的维护治疗选择，并将排毒重新定位为 长期治疗的垫脚石。因此，这些数据可能会提高治疗工作 Ouds并增加获得更大的一线治疗曲目的访问权限。