Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

阿立哌唑和利培酮治疗自闭症的生物标志物 (BAART)

• 批准号: 8321659
• 负责人: C Lindsay LINDSAY DEVANE
• 金额: $ 63.42万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-03 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321659
• 关键词: 17 year old; Academic Medical Centers; Adolescent; Adverse event; Antipsychotic Agents; Autistic Disorder; Behavior; Biological Markers; Biometry; Blinded; Brain-Derived Neurotrophic Factor; Characteristics; Child; Clinical; Clinical Trials; DNA; DSM-IV; Data; Data Analyses; Diagnostic; Double-Blind Method; Dropout; Drowsiness; Drug Monitoring; Epidemiology; FDA approved; Faculty; Gender; Gene Targeting; Genomics; Head; Hospitals; Intervention; Lead; Measures; Medical; Monitor; Multi-Institutional Clinical Trial; Outcome; Patients; Pediatric Hospitals; Pediatrics; Pharmaceutical Preparations; Pharmacogenomics; Phenotype; Placebos; Plasma; Predictive Value; Prolactin; Protocols documentation; Psychiatry; Psychosocial Assessment and Care; Race; Randomized; Randomized Controlled Clinical Trials; Recording of previous events; Research; Research Personnel; Risperidone; Safety; Serum; Single Nucleotide Polymorphism; South Carolina; Symptoms; System; Testing; Therapeutic; Time; Treatment Protocols; Universities; Weight; Weight Gain; Weights and Measures; active method; aripiprazole; atypical antipsychotic; autism spectrum disorder; blind; drug metabolism; evidence base; evidence based guidelines; experience; receptor binding; response; trait; treatment duration

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.

说明（申请人提供）：阿立哌唑和利培酮治疗自闭症的生物标志物（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涉及南卡罗来纳州的三个学术中心，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的专业知识以及药物基因组学研究的专业知识。 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激惹，但关键临床试验中的中等反应率以及对耐受性和体重增加的担忧可能迫使临床医生选择替代药物治疗，而这种药物治疗的循证支持很少。 BAART将在200名5至17岁的自闭症（AD）儿童中评估疗效、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，进行为期10周的利培酮或阿立哌唑双盲随机治疗。 完成研究的应答者可以继续药物治疗三个月。 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）与药物处置和转运、反应和耐受性靶基因相关的各种单核苷酸多态性。 数据分析将允许评估性别、种族和多种生物标志物对两种广泛使用的AD药物干预治疗的临床病程和结局的预测价值。 BAART项目将为AD儿童和青少年药物治疗的选择和监测提供循证指南。 项目叙述：自闭症发生在大约1/150的儿童。 研究者建议开展一项多中心临床试验，为自闭症杜尔格治疗的选择和监测提供循证指导。