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。我们提出了一项多地点研究，其中120名伴有发脾气、攻击和/或自残的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方案（N=80），然后在16周后比较适应性和行为结果。在另外8周的稳定治疗（总共6个月的治疗）后，对利培酮和行为治疗联合表现出积极反应的儿童（估计样本量为60）将被随机分配到继续使用利培酮或逐渐停药的组。停药阶段的目的是检查行为治疗的加入是否允许利培酮的停药。将患有PDD的儿童和青少年纳入研究的理由是基于PDD可能是一种跨社会、情感和学术领域的严重残疾的观察。因此，迫切需要安全有效的PDD新疗法。在RUPP自闭症网络之前的一项研究中，我们表明利培酮对患有自闭症的儿童和青少年是安全有效的，并且伴有发脾气、攻击性和/或自残。我们还发现，在一项安慰剂对照停药研究中，当这些儿科患者停药后，行为症状迅速恢复的比例很高。目前的研究将扩展这些发现，并将测试利培酮和结构化行为治疗方案的组合是否会增强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，以评估特定5 -羟色胺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人群临床试验的设计和实施方面进行合作的能力。此外，这个五站点网络在与PDD儿童临床试验相关的几个措施上建立了可靠性。

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that the behavioral symptoms rapidly returned in a high percentage of these pediatric patients when the medication was withdrawn in a placebo-controlled discontinuation study.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