Repetitive Transcranial Magnetic Stimulation Combined With Motor Rehabilitation Improves Motor and Functional Outcomes After Ischemic Stroke

Official title

Effects of Repetitive Transcranial Magnetic Stimulation Combined With Motor Rehabilitation on Motor and Functional Outcomes in Patients With Ischemic Stroke: A Randomized Sham-Controlled Trial

Overview

Ischemic stroke is a leading cause of long-term motor disability, frequently resulting in hemiplegia and limitations in daily activities and quality of life. Motor rehabilitation is a fundamental component of post-stroke care across all stages of recovery; however, functional outcomes may vary, particularly in patients with persistent motor impairment. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has been used as an adjunct to rehabilitation to modulate cortical excitability and potentially support motor recovery. The purpose of this study is to evaluate the effects of low-frequency rTMS combined with conventional motor rehabilitation compared with sham rTMS combined with conventional motor rehabilitation in patients with first-ever ischemic stroke during the acute, subacute, and chronic stages. Motor function, balance, functional mobility, activities of daily living, and stroke-specific quality of life will be assessed at baseline, after the intervention, and at 3-month and 6-month follow-up.

Detailed description

This study is a randomized, sham-controlled clinical trial designed to evaluate the outcomes of repetitive transcranial magnetic stimulation (rTMS) combined with motor rehabilitation in patients with first-ever ischemic stroke presenting with hemiplegia.Participants will be recruited during the acute (\< 1 month), subacute (1-6 months), and chronic (\> 6 months) stages after stroke onset.

Eligible participants will be allocated into two groups: a control group and an intervention group. Both groups will receive standardized conventional motor rehabilitation targeting upper and lower limb motor function, balance, and functional mobility.

In the intervention group, participants will receive low-frequency rTMS in addition to conventional motor rehabilitation. rTMS will be delivered at a frequency of 1 Hz, once daily, five days per week, for a total of 20 sessions. For upper limb rehabilitation, stimulation will be applied to the primary motor cortex (M1) corresponding to the hand area of the contralesional hemisphere using a figure-of-eight coil. For lower limb rehabilitation, stimulation will target the leg area of M1 located in the medial interhemispheric region using a Hesed coil. Stimulation intensity will be set relative to each participant's motor threshold, and rTMS sessions will be administered immediately prior to motor rehabilitation.

In the control group, participants will receive sham rTMS combined with the same conventional motor rehabilitation program. Sham stimulation will be performed using identical procedures, participant positioning, coil placement, stimulation duration, and acoustic output as the active rTMS condition. To minimize cortical stimulation, the coil will be positioned perpendicular to the scalp, producing minimal magnetic field penetration while maintaining the characteristic clicking sound of the device.

To ensure blinding, participants will not be informed of their group allocation, and they will be instructed not to disclose any information related to the intervention they received prior to outcome assessments. Outcome assessors will be blinded to group assignment.

Outcome measures will be assessed at baseline, immediately after completion of the intervention, and at 3-month and 6-month follow-up to evaluate motor recovery, balance, functional mobility, activities of daily living, and stroke-specific quality of life.

Interventions

• Device Active repetitive transcranial magnetic stimulation
  Active rTMS is delivered at low frequency (1 Hz), 1200 pulses per session, 20 minutes per session, once daily, five days per week, for four consecutive weeks (20 sessions). rTMS is administered immediately prior to the daily conventional rehabilitation session. Upper limb target: Stimulation is applied to the M1 hand area using a figure-of-eight coil. The stimulation site is identified using standard localization methods (EEG 10-20 system landmarks and/or motor evoked potentials when available)
• Device Sham repetitive transcranial magnetic stimulation
  Sham rTMS is administered using the same procedures, participant positioning, coil placement, stimulation duration (20 minutes), and acoustic cues as the active stimulation protocol. To minimize effective cortical stimulation, the coil is oriented perpendicular to the scalp, producing minimal magnetic field penetration while preserving the characteristic clicking sound. Sham sessions follow the same schedule as active rTMS (once daily, five days per week, for four consecutive weeks; 20 sessions)
• Other Conventional motor rehabilitation
  Participants receive standardized conventional motor rehabilitation for 60 minutes per day, five days per week, for four consecutive weeks. Each daily session includes three components: therapeutic exercise (approximately 20 minutes), physical therapy modalities (approximately 20 minutes), and occupational therapy/task-oriented functional training (approximately 20 minutes). The rehabilitation program is identical in content, intensity, and duration for both study arms.

Primary outcome measures

• Change in upper limb motor function assessed by the Fugl-Meyer Assessment for Upper Extremity (FMA-UL) [Time frame: Baseline, immediately after the 4-week intervention period, and at 3-month and 6-month follow-up]

Secondary outcome measures (5)

• Change in manual dexterity assessed by the Box and Block Test (BBT) [Time frame: Baseline, immediately after the 4-week intervention period, and at 3-month and 6-month follow-up]
• Change in functional mobility assessed by the Timed Up and Go test (TUG) [Time frame: Baseline, immediately after the 4-week intervention period, and at 3-month and 6-month follow-up]
• Change in balance performance assessed by the Berg Balance Scale (BBS) [Time frame: Baseline, immediately after the 4-week intervention period, and at 3-month and 6-month follow-up]
• Change in activities of daily living assessed by the modified Barthel Index (mBI) [Time frame: Baseline, immediately after the 4-week intervention period, and at 3-month and 6-month follow-up]
• Change in quality of life assessed by the Stroke-Specific Quality of Life Scale (SS-QoL) [Time frame: Baseline, immediately after the 4-week intervention period, and at 3-month and 6-month follow-up]

Eligibility criteria

Inclusion criteria

• Aged 18 to 80 years.
• Diagnosed with a first-ever ischemic stroke, confirmed by neuroimaging.
• Presence of unilateral hemiparesis attributable to the first-ever ischemic stroke.
• Time since stroke onset:

• Acute stage: < 1 month after stroke onset
• Subacute stage: 1 to 6 months after stroke onset
• Chronic stage: > 6 months after stroke onset
• Moderate neurological impairment, defined as a baseline NIHSS score between 5 and 14.
• Cognitive ability sufficient to understand and follow instructions, indicated by a baseline MMSE score ≥ 20.
• Medically stable and able to participate in a structured motor rehabilitation program.
• Provided written informed consent prior to study enrollment.
• NIHSS and MMSE scores are assessed at baseline only to characterize neurological severity and cognitive status at study entry

Exclusion criteria

• Motor impairment caused by conditions other than ischemic stroke, such as musculoskeletal disorders, traumatic brain injury, Parkinson's disease, encephalitis, or other neurological conditions.
• Contraindications to repetitive transcranial magnetic stimulation, including but not limited to intracranial metallic implants, implanted electronic medical devices (e.g., pacemaker), cochlear implants, known bleeding disorders, pregnancy, history of epilepsy or seizure disorders, severe cardiac disease, severe psychiatric or neurological disorders interfering with participation, or active skin conditions at the stimulation site.
• History of epilepsy or seizure disorders.
• Recurrent stroke occurring during the intervention period.
• Refusal to participate, withdrawal of informed consent, or non-adherence to the intervention protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07369648 · VN-2025-rTMS-MOTOR

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗