Recently completed multi-center clinical trials of adding transcranial direct current stimulation (tDCS) to an efficacy proven form of occupational therapy, modified constraint-induced movement therapy (mCIMT), for post-stroke upper-limb recovery have reported data to suggest that any added benefit at current densities ≤0.114 mA/cm2 is small. This study aimed to evaluate the safety and tolerability of higher-dose bi-hemispheric tDCS (at least 2x the highest current density used in TRANSPORT2 delivered with mCIMT. Methods: We are conducting a 3+3 safety/tolerability/preliminary efficacy dose-escalation study enrolling subjects in the subacute to early chronic stroke phase after a first-ever unihemispheric ischemic stroke with mild-moderate motor impairment with a Fugl-Meyer Upper Extremity scale (FM-UE ≤54) and residual finger/wrist movement. Participants underwent a standardized bi-hemispheric tDCS protocol at 4.5 and 5.0 mA so far (planned escalation up to 8.0 mA) using 5-cm round rubber electrodes at C3/C4 with Ten20 paste (current densities were 0.23 and 0.26 mA/cm2 respectively). The tDCS stimulation started at the same time as mCIMT with 30 minutes of tDCS and 90 minutes of active mCIMT, for 10 sessions delivered over 2 weeks. Visual analog scale (0 = no discomfort; 10 = intolerable) was used for tolerability, and safety monitoring followed the TRANSPORT2 protocol for clinically important adverse events. The change in FM-UE score from baseline to day 15 post-treatment was also measured. The dose escalation continued only if there were no safety or tolerability issues. Results: To date, 6 participants completed treatment (3 at 4.5 mA, 3 at 5.0 mA; mean age 65 ± 10.1 years; 4 females, 2 males). No clinically important adverse events occurred, and dose escalation was well tolerated (all VAS scores between 0-3). The highest total charge density applied was 4.6 C/cm 2 for the 5.0 mA group. The adjusted mean FM-UE improvement exceeded 9 points (mean 14.5 ± SD 2.7 points), more than twice the chosen minimally important clinical difference (MCID) of 4.5 points, a level of recovery rarely seen in after 10 usual/standard therapy sessions. Conclusion: Results from this ongoing study provide preliminary evidence that multiple-sessions of bi-hemispheric tDCS at current densities that are almost 2x as much as those used in the highest dose arm of TRANSPORT2 is safe, tolerable, and may provide a level of improvement at least double the MCID chosen in TRANSPORT2.
Madjidov et al. (Thu,) studied this question.