4/7 Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

4/7 氯氮平预防精神分裂症暴力：一项随机临床试验

• 批准号: 10192468
• 负责人: DEANNA L KELLY
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10192468
• 关键词: Address; Aggressive behavior; Alcohol consumption; Alcohols; Antipsychotic Agents; Behavior; Clinical; Clinical Research; Clinical Trials; Clozapine; Collaborations; Communities; Data; Delusions; Development; Effectiveness; Ensure; Fostering; Future; Hostility; Human Resources; Impulsivity; Individual; Institutes; Intervention; Interview; Link; Magnetic Resonance Imaging; Measures; Multi-Institutional Clinical Trial; Murder; Neurobiology; New York; Outcome; Outcome Measure; Outpatients; Pathway interactions; Patients; Pharmaceutical Preparations; Populations at Risk; Positron-Emission Tomography; Property; Protocols documentation; Psychoses; Psychotic Disorders; Public Health; Randomized; Randomized Clinical Trials; Reporting; Research; Research Domain Criteria; Resources; Risk; Risk Reduction; Running; Safety; Sample Size; Schizophrenia; Self-Injurious Behavior; Site; Symptoms; Syndrome; Testing; Time; Violence; Vulnerable Populations; Work; antisocial behavior; blind; clinical research site; clinically relevant; community setting; effectiveness outcome; effectiveness study; efficacy trial; high risk; improved; individual patient; interest; open label; prevent; primary outcome; psychopathic personality; service delivery; social stigma; substance use; treatment as usual; treatment effect; violence prevention

PROJECT SUMMARY While most people with psychosis are not dangerous and most violence is committed by non-psychotic people, people with psychotic disorders are at increased risk for violence, and violence is associated with worse outcomes and increased stigma. Therefore, decreasing violence risk in psychosis is clinically relevant and has important public health implications. Several clinical studies suggest that clozapine is superior to other antipsychotic medications in reducing violence or aggression. However, there were numerous limitations of these studies including that most of them were observational and non-randomized, included small sample sizes, or focused on hostility, non-physical aggression, or self-harm, rather than violent acts. Further, the majority of these trials were not generalizable to outpatient, community settings. No large effectiveness study has examined the effects of clozapine on violent behavior in community settings. We propose a randomized, parallel-group, 24-week, open-label, single (rater)-blind, 7-site clinical trial to examine the effects of treatment with clozapine vs. treatment as usual (TAU) on the risk of violent acts in 280 individuals with schizophrenia at high risk for violence. This trial will be a collaboration of 7 sites, coordinated by the New York State Psychiatric Institute. The 6 additional collaborating sites contribute unique expertise and will ensure an adequate sample size for this trial. Our primary effectiveness outcome is time to violent acts as measured by the MacArthur Community Violence Interview (MCVI). We will also explore the effects of clozapine on the Point Subtraction Aggression Paradigm. While many factors may contribute to violent behavior in individuals with schizophrenia, including positive symptoms, psychopathy, impulsivity, and substance use, evidence suggests that the final common pathway for many of these disparate causal influences likely runs through behaviors captured by the Excitement Factor of the Positive and Negative Syndrome Scale (i.e., a composite of the scores of excitement, uncooperativeness, poor impulse control, and hostility). Importantly, our target (the excitement factor of the PANSS) has been validated to measure excitement-like symptoms in clinical trials in schizophrenia, is sensitive to treatment, has been linked to the neurobiology of violence in MRI and PET studies, and differentiates clozapine from other antipsychotic drugs. We will also explore the effects of clozapine vs. TAU on positive symptoms (e.g., persecutory delusions) and alcohol and substance use, and how these effects influence the risk for violent acts. To enhance the safe implementation of this study in this vulnerable population at risk of violent behaviors, we will implement clinical safety and treatment engagement protocols that rely upon standard personnel and that will be readily generalizable. This trial will provide guidance on the use of clozapine for violence in community settings and will definitively test hypotheses regarding mechanisms of its anti-violence effects. The results will be immediately relevant to practice and will impact public health because there is currently no standard approach for the treatment of violence in schizophrenia.

项目摘要 虽然大多数精神病患者并不危险，并且大多数暴力是由非精神病患者犯下的，但 患有精神病患者的暴力风险增加，暴力与更糟 结果和污名增加。因此，降低精神病的暴力风险在临床上是相关的，并且 重要的公共卫生影响。几项临床研究表明，氯氮平优于其他 减少暴力或侵略性的抗精神病药物。但是，有许多局限 这些研究包括其中大多数是观察性和非随机化的研究，包括小样本量， 或专注于敌对，非物理侵略或自我伤害，而不是暴力行为。此外，大多数 这些试验无法推广到门诊，社区环境。没有大型有效性研究 研究了氯氮平对社区环境中暴力行为的影响。我们提出了一个随机的， 平行组，24周，开放标签，单个（评估者） - 盲，7位临床试验，以检查治疗的影响 在280名精神分裂症患者中，氯氮平与往常的治疗（TAU）在 暴力的高风险。该试验将是由纽约州精神病学协调的7个网站的合作 研究所。另外6个协作网站贡献了独特的专业知识，并将确保有足够的样本 该试验的尺寸。我们的主要有效性结果是麦克阿瑟衡量的暴力行为的时间 社区暴力访谈（MCVI）。我们还将探索氯氮平对点减法的影响 侵略范式。尽管许多因素可能导致精神分裂症患者的暴力行为，但 证据表明，包括积极症状，精神病，冲动性和药物使用，表明最终 许多这些不同因果影响的常见途径可能是通过由该行为捕获的行为 正综合征和负综合征量表的兴奋因子（即，兴奋得分的综合， 不合作，冲动控制和敌意不足）。重要的是，我们的目标（兴奋因素 PANSS）已经过验证以测量精神分裂症临床试验中的兴奋样症状，是敏感的 要治疗，与MRI和PET研究中的暴力神经生物学有关，并区分 其他抗精神病药的氯氮平。我们还将探索氯氮平与tau对阳性的影响 症状（例如迫害妄想）和酒精和药物的使用，以及这些影响如何影响 暴力行为的风险。为了增强这项研究的安全实施，在这个脆弱的人群中 暴力行为，我们将实施依赖标准的临床安全和治疗参与方案 人员，这将很容易普遍。该试验将为使用氯氮平的使用提供指导 社区环境中的暴力行为，并将明确检验有关其反暴力机制的假设 效果。结果将与实践有关，并将影响公共卫生，因为 目前尚无精神分裂症治疗暴力的标准方法。