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

1/4-RUPP 自闭症网络：胍法辛治疗 PDD 多动症

• 批准号: 7890695
• 负责人: Christopher J McDougle
• 金额: $ 36.6万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7890695
• 关键词: ABCB1 gene; Acute; Address; Adrenergic Agents; Adverse effects; Adverse event; Affect; Age; Algorithms; Aman; 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; Enrollment; Epinephrine; Excretory function; Family; Funding; Genetic; 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; 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; public health relevance; racial and ethnic; randomized trial; response; social group; teacher; urinary

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.

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申请。自闭症是全世界关注的主要公共卫生问题。据估计，仅在美国，残疾的成本每年就超过300亿美元。最近的数据表明，多达50%患有广泛性发育障碍（pdd）的儿童有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，使儿童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，目前还缺乏共识。与典型的ADHD儿童相比，PDD儿童往往表现出较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。我们的试点数据表明，胍法辛是治疗PDD儿童多动症的一种有希望的治疗方法，具有良好的耐受性。此外，我们已经确定了可能与积极作用相关的生物标志物（遗传和神经化学）。基于这些原因，我们选择了胍法辛作为在这一人群中提出的严格和可能确定的研究。该研究包括一项为期8周的随机、双盲、安慰剂对照试验，170名PDD伴有多动和冲动的儿童（5-13岁）服用胍法辛。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（治疗面罩不会被打破）。对于在双盲阶段没有取得积极反应的儿童，治疗盲将被打破。在8周的开放标签期，使用安慰剂治疗无变化或恶化的儿童将接受胍法辛治疗。对胍法辛表现出部分反应的儿童将被随机分配到4周的哌醋甲酯或安慰剂试验中，以评估联合治疗的潜在益处。我们预计将有50名受试者参加这项试点试验。基因变异和尿肾上腺素能/去甲肾上腺素能指标作为生物标志物在调节胍法辛的主要疗效指标和不良反应中的作用将被探讨。