The long-term objectives of this proposal are to utilize pharmacological interventions to improve arousal and recovery in children following TBI.
The specific aims are: 1) Conduct a trial of amantadine therapy in children who have impaired arousal following TBI, 2) Compare the interrater reliability and validity of three different measures of arousal in children with TBI, and 3) Describe the pharmacokinetics of amantadine in children with TBI. The experimental design is a randomized, double- blind, crossover trial of amantadine and placebo. Subjects will include children, ages 5-18 years, admitted to an inpatient rehabilitation unit, who have impaired arousal related to TBI. Each subject will receive three weeks of amantadine and three weeks of placebo, with a one week washout period. Outcome measures will include two standardized measures, the Coma Recovery Scale (CRS) and the Coma/Near Coma Scale (CNCS), and two nonstandardized measures, a physician's clinical assessment of level of consciousness and the family's and physician's subjective evaluation of change in arousal. Each measure will be conducted at baseline and one to three times per week, depending on the measure. A portion of the CRS, the CNCS, and the physician's clinical assessment will be performed by two raters to determine the interrater reliability of each measure. The results of each measure will also be compared in an effort to establish validity. Serum amantadine levels will be obtained at designated times throughout the study and will be analyzed to provide estimates of individual pharmacokinetic parameters, including clearance, half-life, and volume of distribution, as well as non- compartmental parameters. The study results will provide an estimated treatment effect of amantadine in increasing arousal in pediatric TBI and data on the pharmacokinetics of amantadine in children. In addition, potentially useful standardized measures of arousal in children will be identified. This information will be integral in the design of a larger, multi-center study evaluating the efficacy of amantadine in children with TBI.
| Vargus-Adams, Jilda N; McMahon, Mary A; Michaud, Linda J et al. (2010) Pharmacokinetics of amantadine in children with impaired consciousness due to acquired brain injury: preliminary findings using a sparse-sampling technique. PM R 2:37-42 |
| McMahon, Mary A; Vargus-Adams, Jilda N; Michaud, Linda J et al. (2009) Effects of amantadine in children with impaired consciousness caused by acquired brain injury: a pilot study. Am J Phys Med Rehabil 88:525-32 |
