Efficacy of Methylphenidate for Management of Long-term Attention Problems inTBI

哌醋甲酯治疗 TBI 长期注意力问题的疗效

• 批准号: 8725215
• 负责人: Brad G Kurowski
• 金额: $ 13.11万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-22 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725215
• 关键词: 6 year old; Address; Age; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Characteristics; Child; Childhood Injury; Chronic; Clinical; Clinical Management; Clinical Trials; Cognitive; Crossover Design; Development; Dose; Double-Blind Method; Enrollment; Evaluation; Executive Dysfunction; Future; Grant; Health; Individual; Injury; Knowledge; Lead; Literature; Manuscripts; Mediating; Mediator of activation protein; Mentors; Methylphenidate; Morbidity - disease rate; Multi-Institutional Clinical Trial; Neurocognitive; Neuropharmacology; Outcome; Parents; Pharmaceutical Preparations; Placebo Control; Preparation; Prevalence; Protocols documentation; Randomized; Recommendation; Recording of previous events; Research; Risk Factors; Sample Size; Time; Titrations; Training; Traumatic Brain Injury; Treatment Effectiveness; Treatment Efficacy; United States; Work; base; clinical care; disorder subtype; dosage; evidence base; executive function; improved; innovation; mortality; neurobehavioral; novel; pediatric traumatic brain injury; processing speed; public health relevance; response; skills; teacher; treatment response

DESCRIPTION (provided by applicant): Attention deficit hyperactivity disorder (ADHD) is a risk factor for pediatric TBI and often persists post-injury. TBI may also produce attention deficis de novo (secondary ADHD [SADHD]). When combining pre-TBI ADHD and SADHD rates, the prevalence of post-injury ADHD is near 40-45%. First line medication treatment for primary ADHD is methylphenidate, but the use of methylphenidate for attention problems after pediatric TBI is highly variable. Only two clinical trials evaluating the efficacy of methylphenidate on attention problems after pediatric TBI have been performed and the results have been inconclusive. The inconclusive results may be due to limitations of small sample sizes, inadequate dose titration, and inadequate evaluation of potential mediating and moderating factors. This proposal will begin to address these knowledge gaps. The objectives of the study are to (1) determine the efficacy and dose-response of methylphenidate treatment of attention problems after pediatric TBI and (2) provide a better understanding of the relationship of a prior history of ADHD, ADHD subtypes after TBI, executive function, and attentional control to treatment efficacy. The proposed clinical trial will enroll 50 children, age 6-17 years, with attention problems 12-48 months after moderate to severe TBI into a randomized, double-blind, placebo-controlled, cross-over design trial with 3 dose conditions (low, medium, and high). The study will characterize the response of attention problems after pediatric TBI to methylphenidate (primary analysis) and evaluate potential mediating and moderating factors of treatment response (secondary analyses). The study will add new and innovative information to the pediatric TBI literature. It will provide a better understanding of the efficacy of methylphenidate for treatment of attention problems after pediatric TBI and it will elucidate clinical profiles tha may influence response to treatment. The findings have the potential to directly impact clinical management. Findings will also inform the development of larger studies that will facilitate the development of individualized protocols for management of attention problems after pediatric TBI. The study also builds on the candidate's prior research that has evaluated predictors and moderators of cognitive and behavioral outcomes after pediatric TBI. It will provide him with new skills and knowledge that will allow him to move beyond evaluating moderators of outcomes. This proposal will provide the candidate with new expertise in the development, conduct and analysis of clinical trials, improve his knowledge of neuropharmacology, and further develop his knowledge of the assessment of cognitive and behavioral outcomes after pediatric TBI. The candidate's expertise in these areas will be facilitated through a training plan that incorporates didactic course work, directed mentoring, and guidance from his mentoring team on manuscript and future grant preparation. At completion of the project, the candidate will be poised to develop clinical trials to individualize the management of neurobehavioral and cognitive sequelae of pediatric TBI.

描述（由申请人提供）：注意力缺陷多动障碍 (ADHD) 是儿童 TBI 的危险因素，并且通常在受伤后持续存在。 TBI 还可能导致注意力缺陷（继发性 ADHD [SADHD]）。将 TBI 前 ADHD 和 SADHD 发生率结合起来，损伤后 ADHD 的患病率接近 40-45%。原发性 ADHD 的一线药物治疗是哌甲酯，但使用哌甲酯治疗儿童 TBI 后注意力问题的情况差异很大。只有两项临床试验评估了哌醋甲酯对儿童 TBI 后注意力问题的疗效，但结果尚无定论。不确定的结果可能是由于样本量较小、剂量滴定不充分以及对潜在中介和调节因素的评估不充分造成的。该提案将开始解决这些知识差距。该研究的目的是（1）确定哌醋甲酯治疗儿童 TBI 后注意力问题的疗效和剂量反应，以及（2）更好地了解 ADHD 病史、TBI 后 ADHD 亚型、执行能力之间的关系。功能，以及对治疗效果的注意力控制。拟议的临床试验将招募 50 名 6-17 岁、中度至重度 TBI 后 12-48 个月有注意力问题的儿童参加一项随机、双盲、安慰剂对照、交叉设计试验，有 3 种剂量条件（低剂量） 、中、高）。该研究将描述儿科 TBI 后注意力问题对哌醋甲酯的反应（初步分析），并评估治疗反应的潜在中介和调节因素（二次分析）。该研究将为儿科 TBI 文献添加新的创新信息。这将有助于更好地了解哌醋甲酯的功效 用于治疗儿童 TBI 后的注意力问题，并将阐明可能影响治疗反应的临床特征。这些发现有可能直接影响临床管理。研究结果还将为更大规模研究的开展提供信息，这些研究将有助于制定治疗儿科 TBI 后注意力问题的个性化方案。该研究还建立在候选人之前的研究基础上，该研究评估了儿科 TBI 后认知和行为结果的预测因素和调节因素。它将为他提供新的技能和知识，使他能够超越评估结果的调节因素。该提案将为候选人提供临床试验的开发、实施和分析方面的新专业知识，提高他的神经药理学知识，并进一步发展他对儿科 TBI 后认知和行为结果评估的知识。候选人在这些领域的专业知识将通过培训计划得到促进，该计划包括教学课程工作、定向指导以及导师团队对手稿和未来资助准备的指导。该项目完成后，候选人将准备开展临床试验，以个体化治疗儿科 TBI 的神经行为和认知后遗症。