The CONNECT-TBI Trial aims to develop safe, effective treatments for complex mTBI that improve cognitive functioning. Based on the compelling preliminary data generated by our study team, the objective of this study is to conduct a randomized, double-blinded, sham-controlled Phase II clinical trial of APT-3 combined with rTMS, HD-tDCS, or sham to treat cognitive control deficits in Veterans with complex mTBI and PPCS. At the Baseline Visit, participants will undergo demographic, neuropsychological, behavioral, and quality of life testing. They will also undergo structural MRI to permit modeling of their brain, resting/task-related fMRI to identify the CCN, and pseudocontinuous arterial spin labeling (pCASL) and diffusion tensor imaging (DTI) to assess for other pathologies. They will then be randomized to 16 sessions of APT-3 with concurrent rTMS, HD-tDCS, or sham stimulation delivered to the unique functional left dorsolateral prefrontal cortex (DLPFC), a primary node of the CCN. Lastly, they will repeat all baseline tests, and report on 3- and 6-month recovery levels to establish longevity and stability of subjective benefit. Given that this individualization protocol has never been attempted for cognitive rehabilitation in military mTBI, we expect this trial will generate useful effect sizes for HD-tDCS and rTMS to be used for powering the next step, a Phase III multi-center trial.
Age range
18 Years – 59 Years
Sex
ALL
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A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
Primary symptom outcome: Change from baseline in cognitive PCS as measured by the NSI cognitive subscale score at post-treatment.
Timeframe: Baseline and post-treatment visits, 4 weeks
Primary cognitive outcome: Change from baseline in objective cognitive control as measured by accuracy on the Multi-modal Working Memory N-back task (MMWM) to post-treatment Visit.
Timeframe: Baseline and post-treatment visits, 4 weeks
Primary functional outcome: Change from post-treatment visit in overall quality of life as measured by the PGIC at long-term follow-up at 3 and 6 months.
Timeframe: Post-treatment visit and long-term follow-up at 3 and 6 months
Primary imaging outcome: Change (decrease) in CCN activity from Baseline Visit to Post-treatment Visit as measured by the BOLD signal during the MMWM task performance.
Timeframe: Baseline and post-treatment visits, 4 weeks