1/4-RUPP Autism Network: Guanfacine for the Treatment of Hyperactivity in PDD

描述（由申请人提供）：这是一份来自儿童精神药理学研究单位[RUPP]自闭症网络（印第安纳州大学、西雅图儿童研究所、加州大学洛杉矶分校和耶鲁大学）的多中心协作R 01申请。自闭症是全世界的一个主要公共卫生问题。据估计，仅在美国，每年的残疾成本就超过300亿美元。最近的数据表明，多达50%的广泛性发育障碍（PDD）儿童有中度至重度的多动症和冲动问题。这些症状的影响可能是深远的，使孩子不太能够利用教育和行为干预。如何治疗伴有多动症的PDD儿童缺乏共识。与典型的ADHD儿童相比，PDD儿童通常表现出较少的益处和更大的副作用负担。胍法辛通常用于这一人群，但研究很少。我们的试点数据表明，胍法辛是治疗PDD儿童多动症的一种有前途的治疗方法，具有良好的耐受性。此外，我们已经确定了可能与积极影响相关的生物标志物（遗传和神经化学）。由于这些原因，我们选择胍法辛在这一人群中进行严格的和可能确定的研究。该研究包括一项为期8周的随机、双盲、安慰剂对照试验，对170名伴有多动和冲动的PDD儿童（年龄5-13岁）进行胍法辛治疗。显示阳性应答的受试者将被邀请进入8周扩展期（不揭盲治疗）。对于在双盲期未获得阳性应答的儿童，将破盲治疗。在安慰剂组中没有表现出变化或恶化的儿童将在8周的开放标签阶段接受胍法辛治疗。对胍法辛有部分反应的儿童将被随机分配到一个为期4周的哌甲酯或安慰剂的附加试验中，以评估联合治疗的潜在益处。我们预计将有50名受试者进入这项试点试验。将探讨基因变异体和尿肾上腺素能/去甲肾上腺素能指标作为生物标志物在调节胍法辛主要疗效指标和不良反应反应中的作用。 公共卫生相关性：本研究首先对170名伴有多动的广泛性发育障碍儿童进行了胍法辛的随机试验。哌醋甲酯或安慰剂将被添加到儿童谁显示部分受益胍法辛。

DESCRIPTION (provided by applicant): This is a multi-site collaborative R01 application from The Research Units on Pediatric Psychopharmacology [RUPP] Autism Network (Indiana University, Seattle Children's Research Institute, UCLA, and Yale University). Autism is a major public health concern throughout the world. The cost of the disability is estimated to be more than $30 billion annually in the U.S. alone. Recent data indicate that as many as 50% of children with pervasive developmental disorders (PDDs) have moderate to severe problems of hyperactivity and impulsiveness. The impact of these symptoms may be profound and make the child less able to make use of educational and behavioral interventions. Consensus is lacking on how to treat children with PDD accompanied by hyperactivity. Compared to typically developing children with ADHD, children with PDD often show less benefit and greater side effect burden. Guanfacine is commonly used in this population, but poorly studied. Our pilot data indicate that guanfacine is a promising treatment for hyperactivity in children with PDD with a good tolerability profile. In addition, we have identified biomarkers (genetic and neurochemical) that may be associated with positive effects. For these reasons, we chose guanfacine for the proposed rigorous and possibly definitive study in this population. The study involves an 8-week randomized, double-blind, placebo- controlled trial of guanfacine for the 170 children (ages 5-13 years) with PDD accompanied by hyperacti9vity and impulsiveness. Subjects who show a positive response will be invited to enter an 8-week Extension phase (treatment mask will not be broken). The treatment blind will be broken for children who do not achieve a positive response in the Double-blind phase. Children who show no change or deterioration on placebo will be treated with guanfacine in an 8-week Open-label phase. Children who show a partial response to guanfacine will be randomly assigned to a 4-week add on trial of methylphenidate or placebo to evaluate the potential benefits of combined treatment. We expect that 50 subjects will enter this pilot trial. The role of gene variants and urinary adrenergic/noradrenergic measures as biomarkers in moderating response to guanfacine on primary efficacy measures and adverse effects will be explored. PUBLIC HEALTH RELEVANCE: This study begins with a randomized trial of guanfacine in 170 children with Pervasive Developmental Disorders accompanied by hyperactivity. Methylphenidate or placebo will be added for children who show partial benefit to guanfacine.