Background: Stroke is a leading cause of long-term disability worldwide, with over two-thirds of survivors experiencing persistent limb motor dysfunction. Current rehabilitation approaches have limitations in efficacy and accessibility. Blood flow restriction training (BFRT) has shown promise in enhancing muscle strength with low-intensity exercise, while repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability. The combination of these two modalities may produce synergistic effects on motor recovery after stroke.
Objective: This study aims to investigate the effects of BFRT combined with rTMS on upper and lower limb function, muscle strength, balance, and daily living activities in stroke patients with hemiplegia. The primary hypothesis is that the combination therapy will result in greater improvement in upper limb motor function compared to rTMS alone or conventional rehabilitation alone.
Study Design: This is a single-center, randomized, assessor-blind, parallel-group, superiority trial conducted at the Department of Rehabilitation Medicine, First Affiliated Hospital of Zhengzhou University.
Participants: A total of 69 eligible stroke patients with hemiplegia will be enrolled. Inclusion criteria include: confirmed stroke by CT or MRI, age 25-70 years, Brunnstrom stage III or above in both upper and lower limbs, stable vital signs, and ability to understand instructions. Exclusion criteria include: cardiac pacemaker or metal implants, severe cognitive impairment, shoulder subluxation, coagulation disorders, post-stroke epilepsy, and severe organ dysfunction.
Randomization and Blinding: Participants will be randomly assigned in a 1:1:1 ratio to three groups using a random number table generated by an independent researcher. The allocation sequence will be concealed. Outcome assessors and data analysts will be blinded to group assignments. Due to the nature of the interventions, participants and intervention providers cannot be blinded.
Interventions:
Group A (Control): Conventional rehabilitation including medication management, proper positioning, transfer training, conventional limb exercises, physical therapy, and muscle strength training. 30 minutes per session, twice daily, 5 days per week for 4 weeks.
Group B (rTMS): Conventional rehabilitation plus rTMS applied to the M1 area of the affected hemisphere. Stimulation parameters: 10Hz frequency, 90% resting motor threshold, 1200 pulses per session, 15 minutes per session, once daily, 5 days per week for 4 weeks.
Group C (BFRT+rTMS): Conventional rehabilitation plus rTMS (as in Group B) plus BFRT. BFRT is applied using pneumatic cuffs at 60% of arm systolic blood pressure (or limb occlusion pressure) with intermittent occlusion (5 minutes on, 1 minute off) during the same resistance training exercises as Group A. Frequency: 5 days per week for 4 weeks.
Outcome Measures:
Primary Outcome: Change in upper extremity Fugl-Meyer Assessment (FMA-UE) score from baseline to week 4. FMA-UE assesses motor function, reflex activity, and coordination, with scores ranging from 0 to 66 (higher scores indicate better function).
Secondary Outcomes: Changes in Wolf Motor Function Test (WMFT), Modified Barthel Index (MBI), Berg Balance Scale (BBS), root mean square of surface electromyography (sEMG), and safety parameters including D-dimer, fibrinogen, blood pressure, heart rate, and adverse events. All secondary outcomes are assessed at baseline and week 4.
Sample Size Calculation: Based on G\*Power software using repeated measures ANOVA (group × time interaction), with effect size f=0.25, α=0.05, power=90%, 3 groups, 2 measurements, and correlation among repeated measures of 0.5, the calculated total sample size is 54. Accounting for a 20% dropout rate, the final sample size is 69 participants (23 per group).
Statistical Analysis: Primary analysis will be performed on the intention-to-treat (ITT) population using analysis of covariance (ANCOVA) with baseline FMA-UE score, age, and disease duration as covariates. Secondary outcomes will be analyzed using repeated measures ANOVA or non-parametric tests as appropriate. Safety data will be summarized descriptively.
Ethical Considerations: This study will be conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of First Affiliated Hospital of Zhengzhou University. Written informed consent will be obtained from all participants or their legal guardians before enrollment.
