RUPP-PI Project

描述（由申请人提供）：广泛性发育障碍（PDD）是严重的发育状况，影响每1000名学龄儿童中有6名。我们提出了一项多中心研究，其中120名伴有高度易怒行为的PDDs儿童将被随机分配到仅使用利培酮（N=40）或利培酮加结构化行为治疗计划（N=80），并在16周后比较适应和行为结果。在另外8周的稳定期（总共6个月）后，对利培酮和行为疗法的组合显示出阳性应答的儿童（估计样本量为60）将被随机分配至继续利培酮治疗或逐渐停药。停药阶段的目标是检查是否添加行为治疗可以使利培酮停药而不复发。PDD可能是一种跨越社会，情感和学术领域的严重残疾。因此，迫切需要安全有效的PDD新治疗方法。在之前的RUPP自闭症网络研究中，我们表明利培酮对伴有发脾气，攻击和/或自我伤害的自闭症儿童和青少年是安全有效的。我们还发现，在一项安慰剂对照的停药研究中，当停药时，这些儿童患者中有很高比例的人行为症状迅速恢复。本研究将扩展这些发现，并将测试是否利培酮加行为疗法将提高适应功能的儿童与PDDs和防止复发。将仔细监测副作用和治疗反应。将对受试者进行基因分型，以评价特定5-羟色胺受体基因型与治疗应答的关系。拟定的研究将由一个多中心网络进行，该网络已显示出在PDD人群中合作设计和开展临床试验的能力。此外，这五个地点的网络已经建立了与PDD儿童多地点临床试验相关的几项措施的可靠性。 特别行动组还计划开展两项试点研究：（a）在60名患有PDDs和严重ADHD行为的儿童中进行的随机临床试验，（B）在30名患有PDDs和高度易怒行为的儿童和青少年中进行的齐拉西酮研究。

DESCRIPTION (provided by applicant): Pervasive Developmental Disorders (PDDs) are serious developmental conditions affecting 6 per 1000 school-age children. We propose a multisite study in which 120 children with PDDs accompanied by highly irritable behavior will be randomly assigned to risperidone only (N=40) or risperidone plus a structured behavior therapy program (N=80) and compared on adaptive and behavioral outcomes after 16 weeks. After an additional eight weeks of stabilization (6 months total), children who show a positive response to the combination of risperidone and behavior therapy (estimated samples size of 60) will be randomized to continued treatment with risperidone or gradual discontinuation. The goal of the discontinuation phase is to examine whether the addition of behavior therapy permits discontinuation of risperidone without relapse. PDD can be a profound disability across social, emotional, and academic domains. Thus, there is a pressing need for new treatments in PDD that are safe and effective. In a previous RUPP Autism Network study, we showed that risperidone was safe and effective for children and adolescents with autism accompanied by tantrums, aggression, and/or self-injury. We also showed that the behavioral symptoms rapidly returned in a high percentage of these pediatric patients when the medication was withdrawn in a placebo-controlled discontinuation study. The present study will extend these findings and will test whether risperidone plus behavior therapy will enhance adaptive functioning in children with PDDs and protect against relapse. Side effects and therapeutic response will be carefully monitored. Subjects will be genotyped in order to evaluate the relationship of specific serotonin receptor genotypes and treatment response. The proposed study will be conducted by a multisite network that has already shown the capacity to collaborate in the design and conduct of clinical trials in the PDD population. Furthermore, this five-site network has established reliability on several measures relevant to the multi-site clinical trials in children with PDD. O.S.U. also plans two pilot studies: (a) a randomized clinical trial in 60 children with PDDs and severe ADHD behavior and (b) a study of ziprasidone in 30 children and adolescents with PDDs and highly irritable behaviors.