RUPP-PI Program at Yale University

描述（由申请人提供）：广泛性发育障碍（PDD）是一种严重的发育状况，影响学龄儿童中每1000人中有6人。我们提出了一项多中心研究，其中120名伴有发脾气，攻击和/或自伤的PDD儿童将被随机分配到利培酮单独（N=40）或利培酮加结构化行为治疗计划（N=80），然后比较16周后的适应和行为结果。在另外8周的稳定期（总共6个月的治疗）后，对利培酮和行为疗法的组合表现出阳性应答的儿童（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止治疗。停药阶段的目标是检查是否添加行为治疗允许利培酮停药。纳入PDD儿童和青少年的理由是基于观察到PDD可能是社交，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，并将测试利培酮和结构化行为治疗计划的组合是否会增强PDD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。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可靠性的几个措施，相关的临床试验的儿童与PDD的行为。

DESCRIPTION (provided by applicant): Pervasive Developmental Disorders (PDD) are serious developmental conditions affecting 6 per 1000 in school-age children. We propose a multisite study in which 120 children with PDD accompanied by tantrums, aggression, and/or self-injury will be randomly assigned to risperidone only (N=40) or risperidone plus a structured behavior therapy program (N=80) and then compared on adaptive and behavioral outcomes after 16 weeks. After an additional eight weeks of stabilization (6 months of treatment total), children who demonstrate 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. The justification for the inclusion of children and adolescents with PDD is based on the observation that PDD can be a serious 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that the behavioral symptoms rapidly returned in a high percentage of these pediatric patients when the medication was withdrawn in a placebo-controlled discontinuation study.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 the combination of risperidone and a structured behavior therapy program will enhance adaptive functioning in children with PDD 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 that are relevant to the conduct of clinical trials in children with PDD.