Trial Outcomes & Findings for Remediation of Impaired Self-Regulation in Patients With Mild TBI (NCT NCT02260570)

All subjects participated in a single-arm study in which all subjects received tolcapone and placebo in randomized, counterbalanced, crossover fashion. Because baseline dopamine levels can differ substantially between individuals, each subject serves as their own control. As a result, compiling data for a "tolcapone" arm and a "placebo" arm is not preferred, as such a grouping ignores the within-subject comparison. Instead, subjects are grouped "per sequence".

Subjects were screened based on inclusion and exclusion criteria. Only eligible subjects were assigned to a study arm. 55 subjects provided informed consent to participate in screening and study procedures, but after the screening visit, only 35 subjects were determined to be eligible to proceed to study arm assignment.

Remediation of Impaired Self-Regulation in Patients With Mild TBI

Functional MRI measures blood flow changes. Blood Oxygen Level Dependent (BOLD) signals provide an indirect unitless measure of brain activity typically described as a percentage. However, because fMRI data sets are large (\> 10,000 comparisons), analysis packages present results as F statistics or similar measures for individual voxels across the brain. Thus, no single mean or median value describes the 3-way interaction between drug (tolcapone minus placebo), stimulus emotion (neutral versus anxious), and CAPS-score with degrees of freedom = \[1,1,60\]. Because each subject serves as his/her own control, drug results are also intrinsically paired -- i.e. data are presented for participants as tolcapone minus placebo results within subject. The data values below represent the number of above-threshold, neighboring voxels in the largest clusters of voxels in the brain for the patient group as a whole, not separately for each participant.

Tasks to assess cognition were performed while subjects are scanned. Signal detection theory (SDT) assesses the ability of subjects to accurately recall working memory memoranda. In SDT, the sensitivity index d' results from subtracting the normalized false alarm rate from the normalized hit rate; thus, higher values of d' indicate better working memory performance. Here we evaluate the interaction with respect to d' between drug condition (tolcapone minus placebo) and Post-Traumatic Stress Disorder severity as measured by the total score on the \*Clinician Administered PTSD Scale\*, or CAPS. Total CAPS scores range from 0 to 80, with higher scores indicating greater PTSD severity. Because each subject serves as his/her own control, drug results for behavior are intrinsically paired -- i.e. data are presented for participants as tolcapone minus placebo results, as prespecified in the statistical analysis plan.