Treatment of Early Age Mania (TEAM)

描述（由申请人提供）：儿童双相情感障碍（BP-I）是一种严重损害家庭、学校和同伴功能的慢性疾病，并与精神病、混合性躁狂、超电快速循环和自杀的高发生率相关。即使是聪明的孩子在学校也会成绩不及格，大多数都需要服用多种药物。鉴于儿童血压的存在是新认识，目前对治疗的了解还很少，包括对成人血压有效的药物是否会对儿童产生类似的效果。关于治疗，两个更紧迫的问题是（1）首先使用哪类药物（锂、丙戊酸盐、非典型抗精神病药）和（2）如果第一种药物失败，应添加或改用哪种药物。为了调查这些研究问题，TEAM 项目于两年前启动，作为一个复杂、多地点、多层次、均衡分层、适应性策略设计，研究 540 名 6-15 岁儿童 BP-I（躁狂或混合期）受试者。在此范例中，受试者被随机分配到三个层次，其中包括第一层，即未服用研究药物的受试者。第二层是针对对一种研究药物有部分反应的患者的附加策略。第三层是针对一项研究药物失败的患者的交叉递减策略。此外，第一层中部分响应或反应较差的受试者被重新随机分配到其他两个层。由于该设计的新颖性和成本，NIMH 要求 TEAM 开始为期两年的试点，但条件是，如果两年的试点证明了可行性，将鼓励研究人员申请额外四年的资金来完成研究。截至撰写本文时（2004 年 5 月 27 日，提交日期为 2004 年 6 月 7 日），共有 107 名随机受试者，这超出了计划的招募率。此外，所有三个地层都已被填充。因此，可行性已成立。作为一项大型合作协议，这项研究由 NIMH 数据和安全监测委员会 (DSMB) 每季度进行监测。在撰写本文时进行的五次 DSMB 审核中，TEAM 在数据管理、质量控制和安全方面获得了高度赞扬。该合作协议的结构是一个协调站点（圣路易斯华盛顿大学，PI：B. Geller）和五个数据收集站点（儿童国家医疗中心，PI：P. Joshi；约翰霍普金斯大学医疗机构，PI：J. Walkup；匹兹堡大学，PI：D. Axelson；德克萨斯大学加尔维斯顿分校医学分院，PI：K. Dineen Wagner；华盛顿大学圣路易斯分校， PI：J.卢比）。 Ben Vitiello 博士是 NIMH 的科学合作者。首席研究统计学家 Satish lyengar 博士被分包给圣路易斯华盛顿大学的协调中心，Philip Lavori 博士是统计分析的主要顾问。

DESCRIPTION (provided by applicant): Childhood bipolar disorder (BP-I) is a chronic illness that seriously impairs home, school and peer functioning and is associated with high rates of psychosis, mixed mania, ultradian rapid cycling and suicidality. Even bright children get failing grades at school and most require a myriad of medications. Given the newness of recognizing the existence of child BP, there is as yet scant knowledge of treatment, including whether medications that have shown effectiveness in adult BP will have similar effects in children. Regarding treatment, two of the more pressing issues have been (1) which class of drug to use first (lithium, valproate, atypical neuroleptics) and (2) which drug to add-on or switch to if the first drug fails. To investigate these research questions, the TEAM project was initiated two years ago as a complex, multi-site, multi-strata, equipoise stratification, adaptive strategy design to study 540 subjects with child BP-I (manic or mixed phase), aged 6-15. In this paradigm, subjects are randomized within three strata that include Stratum One for those on no study medications. Stratum Two is an add-on strategy for those who are partial responders to one study drug. Stratum Three is a cross-taper strategy for those who have failed one study medication. Also, subjects who are partial or poor responders in Stratum One are re-randomized to the other two strata. Due to the novelty and cost of this design, NIMH requested that TEAM begin as a two year pilot, with the proviso that if the two year pilot demonstrated feasibility, the investigators would be encouraged to apply for an additional four years of funding to complete the study. At the time of this writing (5/27/04 for a 6/7/04 submission date), there are 107 randomized subjects, which exceeds the planned recruitment rate. Furthermore, all three strata are being filled. Therefore, feasibility has been established. As a large cooperative agreement, this study is monitored on a quarterly basis by the NIMH Data and Safety Monitoring Board (DSMB). At the five DSMB audits conducted at the time of this writing, TEAM has received outstanding praise for data management, quality control, and safety. The structure of this cooperative agreement is one coordinating site (Washington U in St. Louis, PI: B. Geller) and five data collection sites (Children's National Medical Center, PI: P. Joshi; Johns Hopkins Medical Institutions, PI: J. Walkup; U Pittsburgh, PI: D. Axelson; UT Medical Branch, Galveston, PI: K. Dineen Wagner; Washington U in St. Louis, PI: J. Luby). Dr. Ben Vitiello is the NIMH scientific collaborator. The chief study statistician, Dr. Satish lyengar is subcontracted to the coordinating site at Washington U in St. Louis and Dr. Philip Lavori is a major consultant for statistical analyses.