2/4-RUPP Autism Network: Guanfacine for the Treatment of Hyperactivity in PDD

2/4-RUPP 自闭症网络：胍法辛治疗 PDD 多动症

基本信息

批准号：
8235066
负责人：
Bryan H King
金额：
$ 17.18万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8235066
关键词：
ABCB1 gene Acute Address Adrenergic Agents Adverse effects Adverse event Affect Age Algorithms Asperger Syndrome Attention deficit hyperactivity disorder Autistic Disorder Behavior Behavior Therapy Biological Markers Blinded Caring Catecholamines Child Childhood Chronic Disease Citalopram Clinical Clinical Trials Cognitive Collaborations Combined Modality Therapy Communication Communities Consensus Data Databases Deterioration Development Diagnosis Diagnostic Disease Dose Double-Blind Method Educational Intervention Enrollment Epinephrine Ethnic group Excretory function Family Funding Genetic Markers Genetic Variation Genotype Guanfacine Health Care Costs Hyperactive behavior Impulsive Behavior Indiana Insurance Intervention Language Lead Masks Measures Medical Mental Health Methods Methylphenidate Monitor Motion Motor Norepinephrine Parents Persons Pervasive Development Disorder Pharmaceutical Preparations Pharmacological Treatment Phase Pilot Projects Placebo Effect Placebos Population Prevalence Productivity Psychopharmacology Public Health Race Randomized Research Research Institute Role Safety Sampling Schools Services Severities Short-Term Memory Site Social Interaction Specific qualifier value Strategic Planning Surveys Symptoms System Testing United States Universities Vaccines Variant adrenergic blind cognitive control combat cost developmental disease disability double-blind placebo controlled trial early childhood evidence base impression improved neurochemistry noradrenergic open label partial response pilot trial programs public health priorities randomized trial response social group teacher urinary

项目摘要

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.

这是儿科精神药理学研究单位 [RUPP] 自闭症网络（印第安纳大学、西雅图儿童研究所、加州大学洛杉矶分校和耶鲁大学）的多站点协作 R01 应用程序。自闭症是全世界的一个主要公共卫生问题。据估计，仅在美国每年因残疾造成的损失就超过 300 亿美元。最近的数据表明，多达 50% 的患有广泛性发育障碍 (PDD) 的儿童存在中度至重度的多动和冲动问题。这些症状的影响可能是深远的，使孩子无法利用教育和行为干预措施。对于如何治疗伴有多动症的 PDD 儿童尚缺乏共识。与患有 ADHD 的正常发育儿童相比，患有 PDD 的儿童通常表现出更少的益处和更大的副作用负担。胍法辛在这一人群中常用，但研究很少。我们的试验数据表明，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，我们还确定了可能与积极作用相关的生物标志物（遗传和神经化学）。出于这些原因，我们选择胍法辛进行针对该人群的严格且可能明确的研究。该研究涉及对 170 名伴有多动和冲动的 PDD 儿童（年龄 5-13 岁）进行为期 8 周的随机、双盲、安慰剂对照胍法辛试验。表现出积极反应的受试者将被邀请进入为期 8 周的延长阶段（治疗面罩不会被破坏）。对于在双盲阶段未达到阳性反应的儿童，将打破治疗盲法。在安慰剂治疗中没有表现出任何变化或恶化的儿童将在为期 8 周的开放标签阶段接受胍法辛治疗。对胍法辛表现出部分反应的儿童将被随机分配接受为期 4 周的哌醋甲酯或安慰剂附加试验，以评估联合治疗的潜在益处。我们预计将有 50 名受试者参加该试点试验。将探讨基因变异和尿肾上腺素能/去甲肾上腺素能测量作为生物标志物在调节对胍法辛的主要疗效测量和不良反应的反应中的作用。