RUPP-PI Project

描述(由申请人提供)：普及性发育障碍(PDDS)是一种严重的发育疾病，每1000名学龄儿童中就有6名受到影响。我们提出了一项多点研究，其中120名伴有高度易怒行为的PDDS儿童将被随机分配到单用利培酮(N=40)或利培酮加结构化行为治疗方案(N=80)，并在16周后比较适应和行为结果。在额外的8周稳定治疗(总共6个月)后，对利培酮和行为疗法(估计样本量为60)的组合表现出阳性反应的儿童将被随机分为继续利培酮治疗或逐步停止治疗。停药阶段的目标是检查行为疗法的增加是否允许利培酮停用而不复发。PDD在社会、情感和学术领域都可能是一种严重的残疾。因此，迫切需要安全有效的PDD新疗法。在之前的RUPP自闭症网络研究中，我们表明利培酮对患有发脾气、攻击性和/或自我伤害的自闭症儿童和青少年是安全有效的。我们还表明，在一项安慰剂对照的停药研究中，当停药时，这些儿科患者中的高比例患者的行为症状迅速恢复。目前的研究将扩展这些发现，并将测试利培酮加行为疗法是否会增强患有PDDS的儿童的适应功能，并防止复发。将仔细监测副作用和治疗反应。受试者将接受基因分型，以评估特定的5-羟色胺受体基因型别与治疗反应的关系。这项拟议的研究将由一个多站点网络进行，该网络已经显示出在PDD人群中合作设计和进行临床试验的能力。此外，这个五个站点的网络在与PDD儿童多站点临床试验相关的几个指标上建立了可靠性。OSU还计划进行两项试验性研究：(A)对60名患有PDDS和严重ADHD行为的儿童进行随机临床试验；(B)对30名患有PDDS和高度易怒行为的儿童和青少年进行齐拉西酮研究。

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that the behavioral symptoms rapidly returned in a high percentage of these pediatric patients when the medication was withdrawn in a placebo-controlled discontinuation study.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.