The safety and feasibility of a pilot randomized clinical trial using combined exercise and neurostimulation for post-stroke pain: the EXERT-Stroke study

Chen Lin ^1,2* Charity J Morgan ¹ E Lane Schlitz Fortenberry ^1,2 X. Michelle ANDROULAKIS ³ Keith McGregor ^1,2

• ¹ University of Alabama at Birmingham, Birmingham, United States
• ² Birmingham VA Medical Center, Birmingham, Alabama, United States
• ³ Ralph H. Johnson VA Medical Center, United States Department of Veterans Affairs, Charleston, South Carolina, United States

Chronic pain after stroke can occur between 10-50% of stroke survivors. Post-stroke pain (PSP) can lead to further complications in a stroke survivor's recovery. PSP is caused by the stroke itself and produces moderate or severe pain. It can manifest as new onset or worsening of prior headaches.EXERT-Stroke was a feasibility pilot 2-arm randomized sham-controlled, double-blind trial at a single center over a 30-day intervention period, followed by a month follow-up. Patients were recruited for this study from July 2022 through June 2024 at the Veterans Hospital. The study protocol was approved by the local institutional review board. The trial was registered with ClinicalTrials.gov (NCT04672044). All potential participants were screened for safety with a graded exercise stress test before randomization. Participants were randomized (1:1) to either active repetitive transcranial magnetic stimulation (rTMS) or sham rTMS. Both arms received the same exercise protocol. The intervention protocol consisted of 10 sessions over a 30-day period of rTMS (sham vs active) + exercise, where rTMS was delivered prior to each exercise session on the same day. RTMS was aimed at the M1 of the contra-lesional hemisphere. Exercise was delivered on a recumbent bicycle targeting a participant's heart rate reserve. Primary outcomes were intervention feasibility (attendance and tolerance) and safety (adverse events).Of those consented, one participant was a screen failure, and nine participants were randomized. The average age was 62 years old, 22.2% were female, and 44.4% were Black. For feasibility, five (55.5%) participants were randomized to active rTMS and four (44.4%) were randomized to sham rTMS. Four of the five (80%) active rTMS and two of the four (50.0%) of the sham rTMS completed the final assessment, suggesting that there was no association between treatment assignment and likelihood of completing the study. Importantly, there were no serious adverse events.This is the first feasibility trial to investigate paired intervention of exercise and rTMS in patients with post-stroke pain. The trial found that the intervention had few safety issues. There was overall positive feedback from participants.