RUPP-PI Project

描述（由申请人提供）： 广泛性发育障碍 (PDD) 是一种严重的发育疾病，每 1000 名学龄儿童中就有 6 人受到影响。我们提出了一项多中心研究，其中 120 名伴有高度烦躁行为的 PDD 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 周后比较适应性和行为结果。再稳定八周（总共 6 个月）后，对利培酮和行为疗法联合治疗显示出阳性反应的儿童（估计样本量为 60）将被随机分配继续利培酮治疗或逐渐停药。停药阶段的目标是检查添加行为疗法是否允许停药而不复发。 PDD 可能是社交、情感和学术领域的严重障碍。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，我们表明利培酮对于伴有发脾气、攻击性和/或自残的自闭症儿童和青少年来说是安全有效的。我们还表明，在一项安慰剂对照停药研究中，当停药时，大部分儿科患者的行为症状迅速恢复。本研究将扩展这些发现，并测试利培酮联合行为疗法是否会增强 PDD 儿童的适应性功能并防止复发。将仔细监测副作用和治疗反应。将对受试者进行基因分型，以评估特定血清素受体基因型与治疗反应的关系。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 人群中设计和进行临床试验方面的合作能力。此外，这个五中心网络已在与 PDD 儿童多中心临床试验相关的多项措施上建立了可靠性。 俄勒冈州立大学还计划开展两项试点研究：(a) 对 60 名患有 PDD 和严重 ADHD 行为的儿童进行随机临床试验；(b) 对 30 名患有 PDD 和高度烦躁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that the behavioral symptoms rapidly returned in a high percentage of these pediatric patients when the medication was withdrawn in a placebo-controlled discontinuation study.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.