Electric Field Navigated 1-Hz rTMS for Poststroke Motor Recovery: The E-FIT Randomized Controlled Trial

Abstract

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1 CL ) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training–related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil. METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1 CL , preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial). The sham coil appearance mimicked the active coil but without the weak electric field in the NICHE trial sham coil. Outcomes measured 1 week, and 1, 3, and 6 months after the end of treatment included the following: upper extremity Fugl-Meyer (primary, 6 months after end of treatment), Action Research Arm Test, National Institutes of Health Stroke Scale, quality of life (EQ-5D), and safety. RESULTS: Of 60 participants randomized, 58 completed treatment and were included for analysis. Bayesian analysis of combined data from the E-FIT and the NICHE trials indicated that active treatment was not superior to sham at the primary end point (posterior mean odds ratio of 1.94 [96% credible interval of 0.61–4.80]). For the E-FIT intent-to-treat population, upper extremity Fugl-Meyer improvement ≥5 pts occurred in 60% (18/30) active group and 50% (14/28) sham group. Participants enrolled 3 to 6 months following stroke had a 67% (31%–91% CI) response rate in the active group at the 6-month end point versus 50% in the sham group (21.5%–78.5% CI). There were significant improvements from baseline to 6 months for both active and sham groups in upper extremity Fugl-Meyer, Action Research Arm Test, and EQ-5D ( P <0.05). Improvement in National Institutes of Health Stroke Scale was observed only in the active group ( P =0.004). Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P =0.72). CONCLUSIONS: Intensive motor rehabilitation 3 to 12 months after stroke improved clinical impairment, function, and quality of life; however, 1 Hz-repetitive transcranial magnetic stimulation was not an effective treatment adjuvant in the present sample population with mixed lesion location and extent. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03010462.