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，与精神病、混合躁狂、超快速循环和自杀率高有关。即使是聪明的孩子在学校也会成绩不及格，而且大多数孩子需要服用无数的药物。由于认识到儿童血压的存在是一件很新的事情，目前关于治疗的知识还很少，包括对成人血压有效的药物是否对儿童也有类似的效果。在治疗方面，两个更紧迫的问题是：(1)首先使用哪一类药物（锂，丙戊酸盐，非典型抗精神病药）和(2)如果第一种药物失败，应该添加或切换哪种药物。为了调查这些研究问题，TEAM项目于两年前启动，作为一个复杂的、多地点、多层次、均衡分层、自适应策略设计，研究了540名6-15岁的儿童BP-I（躁狂或混合期）。在这个范例中，受试者被随机分为三个阶层，其中包括没有服用研究药物的第一阶层。第二阶段是为那些对一种研究药物有部分反应的人提供的附加策略。第三阶段是一个交叉逐渐减少的策略，针对那些已经失败的研究药物。同样，在第一层中部分或较差反应的受试者被重新随机分配到其他两个层。由于这种设计的新颖性和成本，NIMH要求团队从两年的试点开始，附带条件是，如果两年的试点证明了可行性，研究人员将被鼓励申请额外的四年资金来完成研究。在撰写本文时（5/27/04，提交日期为6/7/04），有107个随机受试者，超过了计划的招募率。此外，所有三个地层都在被填满。因此，可行性已经确立。作为一项大型合作协议，该研究由NIMH数据和安全监测委员会（DSMB）每季度监测一次。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卓越的赞誉。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（国家儿童医疗中心，PI: P. Joshi；约翰霍普金斯医疗机构，PI: J. Walkup；匹兹堡大学，PI: D. Axelson；加尔维斯顿UT医学分部，PI: K. Dineen Wagner；圣路易斯华盛顿大学，PI: J. Luby）。本·维蒂洛博士是NIMH的科学合作者。首席研究统计学家Satish lyengar博士被转包到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.