Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

描述（由申请人提供）：阿立哌唑和利培酮治疗的自闭症生物标志物（BAART）项目将为自闭症药物治疗的选择和监测提供循证指导。BAART涉及南卡罗莱纳的三个学术中心，这些中心拥有自闭症谱系障碍患者表型分析、临床试验中评估患者反应和药物基因组学研究方面的专业知识。尽管FDA已经批准使用抗精神病药物利培酮治疗与自闭症相关的易怒，但关键临床试验的中等反应率，以及对耐受性和体重增加的担忧，迫使临床医生选择替代药物治疗，而基于证据的支持很少。BAART将评估200名5 - 17岁自闭症儿童（AD）的疗效、耐受性和安全性的预测因素，在为期两周的单盲安慰剂期后，采用利培酮或阿立哌唑进行为期10周的随机双盲治疗。完成研究的应答者可以继续进行三个月的药物治疗。考虑的因素包括：1)精神病史；2)症状反应；3)社会心理支持；4)公差措施；5)血清催乳素、脑源性神经营养因子浓度；6)与药物处置、转运、反应和耐受性相关的靶基因的多种单核苷酸多态性。数据分析将允许评估性别、种族和多种生物标志物对临床过程和两种广泛使用的阿尔茨海默病药物干预治疗结果的预测价值。BAART项目将为患有AD的儿童和青少年的药物治疗选择和监测提供循证指南。

DESCRIPTION (Provided by Applicant): The Biomarkers in autism of aripiprazole and risperidone treatment (BAART) project will provide evidence-based guidance in the selection and monitoring of drug treatment of autism. BAART involves three academic centers across South Carolina, with expertise in phenotyping patients with autistic spectrum disorders, assessing patient response in clinical trials, and expertise in pharmacogenomic research. Although the FDA has approved use of the antipsychotic drug risperidone for irritability associated with autistic disorder, a moderate response rate in pivotal clinical trials and concerns over tolerability and weight gain can force clinicians to select alternative drug treatments, for which evidence-based support is sparse. BAART will assess predictors of efficacy, tolerability, and safety in 200 children five to seventeen years old with autistic disorder (AD) during a double-blind, randomized ten week treatment period with either risperidone or aripiprazole following a two-week single-blind placebo period. Responders who complete the study may continue with medication treatment for three months. Factors considered will include 1) psychiatric history; 2) symptom response; 3) psychosocial support; 4) measures of tolerability; 5) serum prolactin and brain-derived neurotrophic factor concentration; and 6) a variety of single nucleotide polymorphisms related to target genes for drug disposition and transport, response, and tolerability. Data analysis will allow assessment of gender, race, and multiple biomarkers for their predictive value on the clinical course and outcome to treatment with two widely used pharmacologic interventions for AD. The BAART project will result in evidence-based guidelines for selection and monitoring of drug treatment of children and adolescents with AD. PROJECT NARRATIVE: Autism occurs in approximately 1 in 150 children. The investigators propose a multi-center clinical trial to provide evidence-based guidance in the selection and monitoring of durg treatment of autism.