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.

Public Health Relevance

Attention problems after traumatic brain injury (TBI) in children often lead to difficulties in multiple settings. This project will determine the effectiveess of methylphenidate for treatment of long-term attention problems after pediatric TBI. The influence of clinical characteristics of attention problems on treatment effectiveness will also be evaluated. Findings from the study have the potential to directly impact clinical care.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HD074683-02
Application #
8725215
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Michel, Mary E
Project Start
2013-08-22
Project End
2018-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$131,085
Indirect Cost
$9,710
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Yuan, Weihong; Wade, Shari L; Quatman-Yates, Catherine et al. (2017) Structural Connectivity Related to Persistent Symptoms After Mild TBI in Adolescents and Response to Aerobic Training: Preliminary Investigation. J Head Trauma Rehabil 32:378-384
Wade, Shari L; Cassedy, Amy E; Fulks, Lauren E et al. (2017) Problem-Solving After Traumatic Brain Injury in Adolescence: Associations With Functional Outcomes. Arch Phys Med Rehabil 98:1614-1621
Dexheimer, Judith W; Kurowski, Brad G; Anders, Shilo H et al. (2017) Usability evaluation of the SMART application for youth with mTBI. Int J Med Inform 97:163-170
Haarbauer-Krupa, Juliet; Ciccia, Angela; Dodd, Jonathan et al. (2017) Service Delivery in the Healthcare and Educational Systems for Children Following Traumatic Brain Injury: Gaps in Care. J Head Trauma Rehabil 32:367-377
Kurowski, Brad G; Hugentobler, Jason; Quatman-Yates, Catherine et al. (2017) Aerobic Exercise for Adolescents With Prolonged Symptoms After Mild Traumatic Brain Injury: An Exploratory Randomized Clinical Trial. J Head Trauma Rehabil 32:79-89
Kurowski, Brad G; Treble-Barna, Amery; Zang, Huaiyu et al. (2017) Catechol-O-Methyltransferase Genotypes and Parenting Influence on Long-Term Executive Functioning After Moderate to Severe Early Childhood Traumatic Brain Injury: An Exploratory Study. J Head Trauma Rehabil 32:404-412
Babcock, Lynn; Kurowski, Brad G; Zhang, Nanhua et al. (2017) Adolescents with Mild Traumatic Brain Injury Get SMART: An Analysis of a Novel Web-Based Intervention. Telemed J E Health 23:600-607
Treble-Barna, Amery; Zang, Huaiyu; Zhang, Nanhua et al. (2016) Does Apolipoprotein e4 Status Moderate the Association of Family Environment with Long-Term Child Functioning following Early Moderate to Severe Traumatic Brain Injury? A Preliminary Study. J Int Neuropsychol Soc 22:859-64
Evanson, Nathan K; Paulson, Andrea L; Kurowski, Brad G (2016) A Narrative Review of Pharmacologic and Non-pharmacologic Interventions for Disorders of Consciousness Following Brain Injury in the Pediatric Population. Curr Phys Med Rehabil Rep 4:56-70
Kurowski, Brad G; Backeljauw, Barynia; Zang, Huaiyu et al. (2016) Influence of Catechol-O-methyltransferase on Executive Functioning Longitudinally After Early Childhood Traumatic Brain Injury: Preliminary Findings. J Head Trauma Rehabil 31:E1-9

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