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This randomized controlled trial aims to evaluate whether combining blood flow restriction training (BFRT) with repetitive transcranial magnetic stimulation (rTMS) improves limb function in stroke patients with hemiplegia. A total of 69 participants will be randomly assigned to three groups: conventional rehabilitation alone (control group), conventional rehabilitation plus rTMS, or conventional rehabilitation plus BFRT combined with rTMS. The intervention period is 4 weeks, with assessments conducted at baseline and at the end of treatment. The primary outcome is the change in upper extremity Fugl-Meyer Assessment (FMA-UE) score, which measures motor function recovery. Secondary outcomes include Wolf Motor Function Test, Modified Barthel Index for daily activities, Berg Balance Scale, and safety parameters such as coagulation markers and adverse events. This study will help determine whether this combined approach offers a more effective rehabilitation strategy for stroke survivors.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional Rehabilitation Group | Active Comparator | Participants receive conventional rehabilitation including medication management, proper positioning, transfer training, conventional upper and lower limb exercises (anti-spasm, isolated movement training), physical therapy, and muscle strength training. Interventions are administered 30 minutes per session, twice daily, 5 days per week for 4 weeks. |
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| rTMS Group | Experimental | In addition to conventional rehabilitation as described in Arm A, participants receive repetitive transcranial magnetic stimulation (rTMS). Stimulation is applied to the M1 area of the affected hemisphere at 90% of resting motor threshold (RMT), with frequency of 10Hz, 1200 pulses per session, 15 minutes per session, once daily, 5 days per week for 4 weeks. |
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| BFRT + rTMS Group | Experimental | In addition to conventional rehabilitation and rTMS as described in Arm B, participants receive blood flow restriction training (BFRT). BFRT is applied using pneumatic cuffs at 60% of arm systolic blood pressure (or limb occlusion pressure). The resistance training protocol is identical to Arm A (shoulder and quadriceps exercises). Training pattern: 5 minutes of occlusion followed by 1 minute of release. Frequency: 5 days per week for 4 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Conventional Rehabilitation | Other | Conventional rehabilitation includes medication management, proper positioning (supine, healthy side lying, affected side lying), transfer training (lateral transfer, turning, sitting up), conventional upper and lower limb exercises (anti-spasm exercises, isolated movement training, inhibition of flexion spasm of metacarpophalangeal joints and ankle joints), passive movement, techniques to induce active muscle contraction, physical therapy (low-frequency stimulation, medium-frequency stimulation, ultrashort wave, electroacupuncture), and muscle strength training (shoulder flexion, extension, adduction, abduction, internal/external rotation, elbow flexion/extension for upper limbs; hip abduction, quadriceps stretching, quadriceps press, squats, straight leg raise for lower limbs). Duration: 30 minutes per session, twice daily, 5 days per week for 4 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Upper Extremity Fugl-Meyer Assessment (FMA-UE) | FMA-UE is a stroke-specific, performance-based measure of upper limb motor impairment. It assesses reflex activity, movement control, and muscle strength in the shoulder, elbow, forearm, wrist, and hand. Total score ranges from 0 to 66, with higher scores indicating better motor function. | Baseline and 4 weeks (end of intervention) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Wolf Motor Function Test (WMFT) score | The Wolf Motor Function Test is a timed and functional ability-based measure of upper extremity motor ability. It consists of 15 timed tasks and 2 strength tasks. For timed tasks, scores range from 0 to 120 seconds, with lower scores indicating better function. For functional ability, scores range from 0 to 5, with higher scores indicating better movement quality. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Shenao Du | Contact | +86 18338275745 | 18338275745@163.com |
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Individual participant data will not be shared because the study is a single-center exploratory trial with a small sample size, and the informed consent obtained from participants did not include provisions for data sharing with external researchers. Additionally, there are no dedicated resources to prepare and maintain anonymized datasets for public sharing.
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| Repetitive Transcranial Magnetic Stimulation (rTMS) | Device | rTMS is applied to the M1 area of the affected hemisphere. The resting motor threshold (RMT) is determined first. Stimulation parameters: frequency 10 Hz, intensity 90% RMT, 1200 pulses per session, 15 minutes per session, once daily, 5 days per week for 4 weeks. Device: Magstim Rapid2 or similar transcranial magnetic stimulator. |
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| Blood Flow Restriction Training (BFRT) | Device | BFRT is performed using pneumatic cuffs (arm cuff: 68×7.5 cm; leg cuff: 109×10 cm) with a pressure display. Before first use, a warm-up of five cycles of inflation/deflation to 100 mmHg (20 sec inflation, 9 sec deflation) is conducted. Pressure is set at 60% of arm systolic blood pressure (SBP) for the upper limb, applied 2 cm below the axilla; for the lower limb, pressure is set at 60% of limb occlusion pressure, applied at the proximal thigh. During occlusion, patients perform the same resistance training exercises as described in Conventional Rehabilitation (shoulder and quadriceps exercises). Occlusion pattern: 5 minutes of occlusion followed by 1 minute of release. Training frequency: 5 days per week for 4 weeks. Device: BFR training system by Theratools or similar. |
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| Baseline, 4 weeks |
| Change in Modified Barthel Index (MBI) | The Modified Barthel Index is a measure of independence in activities of daily living, including feeding, bathing, grooming, dressing, bowel and bladder control, toilet use, transfers, mobility, and stairs. Total score ranges from 0 to 100, with higher scores indicating greater independence. | Baseline, 4 weeks |
| Change in root mean square (RMS) of surface electromyography (sEMG) | Surface electromyography (sEMG) records the electrical activity of muscles during contraction. The root mean square (RMS) value reflects the amplitude of muscle activation, measured in microvolts (μV). Higher RMS values indicate greater muscle recruitment and activation. Measurements are taken from key upper and lower limb muscles during standardized maximal voluntary contractions. Changes from baseline to week 4 are reported. | Baseline, 4 weeks |
| Change in Berg Balance Scale (BBS) score | The Berg Balance Scale is a 14-item measure of static and dynamic balance ability in adults. Each item is scored from 0 to 4, with a total score ranging from 0 to 56. Higher scores indicate better balance and lower fall risk. Changes from baseline to week 4 are reported. | Baseline, 4 weeks |
| Change in D-dimer levels | D-dimer is a fibrin degradation product present in blood after a blood clot is degraded by fibrinolysis. It is measured in mg/L or μg/L FEU (fibrinogen equivalent units). Elevated levels may indicate thrombosis, which is a potential safety concern for blood flow restriction training. Normal reference range is typically <0.5 mg/L. Values are assessed at screening and at week 4 (or when adverse events occur) to monitor for thrombotic events. | Screening, 4 weeks (if adverse events occur |
| Change in fibrinogen levels | Fibrinogen is a glycoprotein synthesized by the liver that plays a key role in blood coagulation. It is measured in g/L. Normal reference range is typically 2.0-4.0 g/L. Changes in fibrinogen levels are monitored as a safety measure for potential coagulation abnormalities related to blood flow restriction training. Values are assessed at screening and at week 4 (or when adverse events occur). | Screening, 4 weeks (if adverse events occur) |
| ncidence of treatment-emergent adverse events | An adverse event (AE) is any untoward medical occurrence in a participant administered the study interventions, which does not necessarily have a causal relationship with the interventions. Treatment-emergent adverse events are those that occur or worsen after the start of the intervention. All AEs are recorded and assessed for severity (mild, moderate, severe) and relationship to the study interventions (unrelated, possibly related, probably related, definitely related). Serious adverse events (SAEs) are defined as any event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or requires intervention to prevent permanent impairment or damage. Incidence rates are reported for all AEs, SAEs, and AEs leading to discontinuation. Safety monitoring continues throughout the 4-week intervention period and 4-week follow-up (total 8 weeks). | Up to 8 weeks |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D006429 | Hemiplegia |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010243 | Paralysis |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| D000090003 | Blood Flow Restriction Therapy |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
| D005791 | Patient Care |
| D026741 | Physical Therapy Modalities |
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