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、混合躁狂、超昼夜快速循环和自杀倾向的高发率相关。即使是聪明的孩子在学校也会成绩不及格，大多数需要无数的药物治疗。由于认识到儿童BP的存在是新的，因此对治疗的了解还很少，包括对成人BP有效的药物是否会对儿童产生类似的影响。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，则添加或转换为哪种药物。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，平衡分层，适应性策略设计，研究540名儿童BP-I（躁狂或混合期），年龄6-15岁。在该范例中，受试者在三个分层中被随机化，其中包括分层1（未接受研究药物的受试者）。第二层是对一种研究药物有部分应答者的附加策略。第三层是一种交叉递减策略，适用于一种研究药物治疗失败的患者。此外，将第一层中的部分或不良应答者重新随机分配至其他两个层。由于这种设计的新奇和成本，NIMH要求TEAM开始作为两年的试点，附带条件是，如果两年的试点证明可行性，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（2004年5月27日，提交日期为2004年6月7日），有107例随机化受试者，超过了计划招募率。此外，这三个层次都在填补。因此，可行性已经确立。作为一项大型合作协议，NIMH数据和安全性监测委员会（DSMB）每季度对本研究进行一次监测。在撰写本文时进行的五次DSMB稽查中，TEAM在数据管理、质量控制和安全性方面获得了出色的赞誉。该合作协议的结构是一个协调中心（华盛顿U圣路易斯，PI：B。Geller）和五个数据收集站点（儿童国家医疗中心，PI：P. Joshi;约翰霍普金斯医疗机构，PI：J. Walkup; U匹兹堡，PI：D。Axelson; UT医疗分支，加尔维斯顿，PI：K。迪宁瓦格纳;华盛顿U在圣路易斯，PI：J.吕比）。Ben Vitiello博士是NIMH的科学合作者。主要研究统计学家Satish lyengar博士分包给圣路易斯华盛顿U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.