Measuring and Predicting Responses to ATX and MPH

测量和预测对 ATX 和 MPH 的反应

• 批准号: 7329792
• 负责人: MARK A STEIN
• 金额: $ 37.76万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-04 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7329792
• 关键词: Adherence; Adolescent; Adverse effects; Alleles; Attention deficit hyperactivity disorder; Characteristics; Child; Clinical; Comorbidity; Cross-Over Studies; Crossover Design; DRD4 gene; Data; Disease; Dose; Double-Blind Method; End Point; Family; Genotype; Impairment; Individual; Individual Differences; Lead; Measures; Methylphenidate; Neurobiology; Numbers; Outcome; Patients; Pharmacogenetics; Placebo Control; Preparation; Public Health; Randomized; Relative (related person); Reporting; Research Personnel; Residual state; Safety; Severities; Site; Subgroup; Symptoms; Testing; Work; Youth; atomoxetine; burden of illness; clinical research site; comparative; desire; experience; functional disability; programs; psychostimulant; response; size

DESCRIPTION (provided by applicant): ADHD is one of the most frequently occurring disorders of children and adolescents, and represents a significant public health problem. A plethora of scientific data documents the robust efficacy [dj1]and safety of psycho stimulants for the management of ADHD symptoms and associated impairments. However, there is also considerable variability in response, with many individuals reporting lower levels of tolerability and palatability. Moreover, only a subgroup of those receiving stimulant treatments achieves a response that approximates normal functioning. The recent approval of atomoxetine (ATX) offers a non-stimulant alternative for the treatment of ADHD. ATX is structurally unrelated to the stimulants and appears to work via a different mechanism. Thus, ATX may be an effective treatment for those who cannot tolerate stimulants or who have an inadequate response, and responders to the two treatments may have different clinical and neurobiological characteristics. This two-site study will evaluate the relative efficacy, tolerability and palatability of Concerta methylphenidate (MPH) and ATX in the treatment of children and adolescents with ADHD, using a randomized, double blind, crossover design. To date, no study has compared the leading stimulant and non-stimulant treatments in large numbers of youth, using the most effective doses for each treatment, and evaluating response to both treatments in the same individuals. We will test the hypothesis that MPH and ATX have similar overall efficacy in 320 children, with sufficient statistical power to detect even a small effect size difference between the treatments. We will examine "normalization" of response, as well as more traditional outcomes, because the former more closely reflects the desired endpoint of treatment. We will additionally evaluate the potential moderating effects of genotype. We hypothesize that regardless of group differences in efficacy in ADHD symptom reduction, there will be differential response and tolerability within individuals, which will be associated with distinct neurobiological characteristics. These data will be vitally important to patients, families, and clinicians in identifying those factors within individuals that predict optimal response to the two treatments, and lead to a reduction in burden of illness for youth with ADHD and their families.

描述（由申请人提供）：ADHD是儿童和青少年最常见的疾病之一，是一个重大的公共卫生问题。大量的科学数据证明了精神兴奋剂在治疗ADHD症状和相关损伤方面的强大功效和安全性。然而，反应也存在相当大的差异，许多个体报告耐受性和适口性水平较低。此外，只有一个接受兴奋剂治疗的亚组达到了接近正常功能的反应。最近批准的托莫西汀（ATX）为治疗ADHD提供了一种非兴奋剂替代品。ATX在结构上与兴奋剂无关，似乎通过不同的机制起作用。因此，ATX可能是一种有效的治疗那些谁不能耐受兴奋剂或谁有一个不充分的反应，和两种治疗的反应者可能有不同的临床和神经生物学特征。这项双中心研究将采用随机、双盲、交叉设计，评价Concerta哌甲酯（MPH）和ATX治疗ADHD儿童和青少年的相对疗效、耐受性和适口性。到目前为止，还没有研究比较了大量年轻人的主要兴奋剂和非兴奋剂治疗，使用每种治疗的最有效剂量，并评估了同一个体对两种治疗的反应。我们将在320名儿童中检验MPH和ATX具有相似的总体疗效的假设，具有足够的统计功效来检测治疗之间即使很小的效应量差异。我们将研究反应的“正常化”以及更传统的结果，因为前者更接近于反映治疗的预期终点。我们还将评估基因型的潜在调节作用。我们假设，无论ADHD症状减轻疗效的组间差异如何，个体内的反应和耐受性都存在差异，这与不同的神经生物学特征相关。这些数据对于患者，家庭和临床医生确定预测两种治疗最佳反应的个人因素至关重要，并导致ADHD青少年及其家庭的疾病负担减轻。