Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

描述(申请人提供)：阿立哌唑和利培酮治疗自闭症的生物标记物(BART)项目将为自闭症药物治疗的选择和监测提供循证指导。Baart涉及南卡罗来纳州的三个学术中心，拥有自闭症谱系障碍患者的表型鉴定、临床试验中评估患者反应以及药物基因组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过敏性疾病，但在关键的临床试验中，适度的应答率以及对耐受性和体重增加的担忧可能会迫使临床医生选择替代药物治疗，而对这些治疗方法的循证支持很少。BART将评估200名5至17岁自闭症(AD)儿童的疗效、耐受性和安全性的预测因素。在为期两周的单盲安慰剂治疗后，BART将对利培酮或阿立哌唑进行为期十周的双盲随机治疗。完成研究的应答者可以继续接受三个月的药物治疗。考虑的因素包括1)精神病史；2)症状反应；3)心理社会支持；4)耐受性测量；5)血清催乳素和脑源性神经营养因子浓度；6)与药物处置和运输、反应和耐受性目标基因有关的各种单核苷酸多态。数据分析将允许评估性别、种族和多个生物标记物对两种广泛使用的AD药物干预治疗的临床过程和结果的预测价值。Baart项目将为选择和监测患有阿尔茨海默病的儿童和青少年的药物治疗制定循证指导方针。 项目简介：大约每150名儿童中就有1人患有自闭症。研究人员建议进行一项多中心临床试验，为自闭症药物治疗的选择和监测提供循证指导。

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.