Efficacy of Personalized Repetitive Transcranial Magnetic Stimulation Protocol Based on Functional Reserve to Enhance Upper Limb Function in Subacute Stroke Patients

Efficacy of Personalized Repetitive Transcranial Magnetic Stimulation Protocol Based on Functional Reserve to Enhance Upper Limb Function in Subacute Stroke Patients: A Multi Center, Randomized, Single Blind, Parallel Group Prospective Clinical Trial

The objective of this study was to determine the effects of protocols of repetitive transcranial magnetic stimulation (rTMS) therapy based on the functional reserve of each hemiplegic stroke patient in subacute phase, compared to conventional low-frequency rTMS therapy on contralateral M1. Investigators hypothesized that the functional reserve of each hemiplegic stroke patient will be different, and therefore an appropriate simulating target for rTMS therapy is needed. In addition, this approach could be more effective compared to conventional protocols applied to stroke patients regardless of their severity, predicted mechanism of motor function recovery, or functional reserves.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: High-Frequency1; Device: cTBS1; Device: High-Frequency2; Device: cTBS2; Device: High-Frequency3; Device: cTBS3

Detailed Description

rTMS treatment for patients with stroke is traditionally based on interhemispheric interactions. The widely-used traditional rTMS treatment protocol involves inhibitory low-frequency or continuous theta burst stimulation (cTBS) applied over the contralesional hemisphere and excitatory high-frequency stimulation over the ipsilesional hemisphere. However, concerns have arisen regarding the effect of rTMS on motor recovery in stroke patients. Although still subject to debate, a possible reason for the diverse results of rTMS applied to stroke patients is the uniform application protocol to individuals with varying pathologies and functional reserves, aimed at enhancing recovery.

Therefore, this study was aimed to determine the effects of protocols of rTMS therapy based on the functional reserve of each hemiplegic stroke patient.

Based on screening evaluations (TMS-induced motor evoked potential (MEP), diffusion tensor imaging (DTI), MRI), investigators hypothesized that patients could be categorized into three groups: 1) preserved ipsilateral corticospinal tract, 2) preserved ipsilateral alternative corticospinal tract, and 3) no ipsilateral corticospinal tract preserved. For each group, investigators plan to randomly assign patients to experimental and control groups to demonstrate the efficacy of different rTMS protocols based on functional reserves compared to conventional inhibitory rTMS applied to the contralesional primary motor cortex.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Won Hyuk Chang, PhD; Phone Number: 82-2-3410-6068; Email: wh.chang@samsung.com
• Study Contact Backup: Name: Ho Seok Lee, PhD; Phone Number: 82-2-3410-2810; Email: hoseok89.lee@samsung.com

Study Locations

• South Korea
  • Seoul, South Korea, 06351
    • Recruiting
    • Samsung Medical Center
    • Contact: Won Hyuk Chang, PhD; Phone Number: +82-2-3410-6068; Email: wh.chang@samsung.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. hemiplegic stroke patients in the subacute phase (7 days to 3 months from the onset) who are currently hospitalized,
2. FMA score of the upper extremity ≤42,
3. adequate language and cognitive function to perform at least a 1-step obey-command,
4. pre-stroke functional level of modified Rankin Scale (mRS) ≤1,
5. aged ≥19 years old,
6. patients willing to sign the informed consent.

Exclusion Criteria:

1. those with contraindications to rTMS, such as epilepsy, implanted metal objects in the head, or a history of craniotomy,
2. those with progressive of hemodynamically unstable medical conditions,
3. those with coexisting neurological conditions, such as spinal cord injury or Parkinson's disease,
4. those with major psychiatric disorders, such as major depression, schizophrenia, or dementia,
5. those having contraindications to conduct an MRI study,
6. those who are pregnant or lactating ,
7. patients who have refused to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Frequency1; Confirmed responses in TMS-induced MEP: Preserved ipsilateral corticospinal tract. High-frequency rTMS over ipsilateral primary motor cortex will be applied.	Device: High-Frequency1; rTMS intervention: 20 sessions of 10-Hz rTMS at 90% resting motor threshold (RMT), 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: ipsilateral primary motor cortex. Total rTMS sessions: once a day, 5 days per week, for 2 weeks, totaling 10 sessions. Additional treatment: inpatient conventional rehabilitation therapy, consisting of occupational and physical therapy for 30 minutes each, twice daily, for 2 weeks, as well as the routine pharmacotherapy based on the guidelines for management of patients with stroke.
Active Comparator: cTBS1; Confirmed responses in TMS-induced MEP: Preserved ipsilateral corticospinal tract. continous Theta Burst Stimulation (cTBS) protocol of rTMS over contralateral primary motor cortex will be applied.	Device: cTBS1; rTMS intervention: 40 seconds of cTBS at 70% RMT, totaling 600 pulses. rTMS target: contralateral primary motor cortex. Total rTMS sessions: once a day, 5 days per week, for 2 weeks, totaling 10 sessions. Additional treatment: inpatient conventional rehabilitation therapy, consisting of occupational and physical therapy for 30 minutes each, twice daily, for 2 weeks, as well as the routine pharmacotherapy based on the guidelines for management of patients with stroke.
Experimental: High-Frequency2; Absent responses in TMS-induced MEPs, but confirmed corticospinal tract integrity in DTI; Preserved ipsilateral alternative corticospinal tract. High-frequency rTMS over ipsilateral premotor cortex will be applied.	Device: High-Frequency2; rTMS intervention: 20 sessions of 10-Hz rTMS at 90% RMT, 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: ipsilateral premotor cortex. Total rTMS sessions: once a day, 5 days per week, for 2 weeks, totaling 10 sessions. Additional treatment: inpatient conventional rehabilitation therapy, consisting of occupational and physical therapy for 30 minutes each, twice daily, for 2 weeks, as well as the routine pharmacotherapy based on the guidelines for management of patients with stroke.
Active Comparator: cTBS2; Absent responses in TMS-induced MEPs, but confirmed corticospinal tract integrity in DTI; Preserved ipsilateral alternative corticospinal tract. continous Theta Burst Stimulation (cTBS) protocol of rTMS over contralateral primary motor cortex will be applied.	Device: cTBS2; rTMS intervention: 40 seconds of cTBS at 70% RMT, totaling 600 pulses. rTMS target: contralateral primary motor cortex. Total rTMS sessions: once a day, 5 days per week, for 2 weeks, totaling 10 sessions. Additional treatment: inpatient conventional rehabilitation therapy, consisting of occupational and physical therapy for 30 minutes each, twice daily, for 2 weeks, as well as the routine pharmacotherapy based on the guidelines for management of patients with stroke.
Experimental: High-Frequency3; Absent responses in all ipsilateral corticospinal tract. High-frequency rTMS over contralateral primary motor cortex will be applied.	Device: High-Frequency3; rTMS intervention: 20 sessions of 10-Hz rTMS at 90% RMT, 50 pulses per session with a 25-second interval between sessions, totaling 1,000 pulses. rTMS target: contralateral primary motor cortex. Total rTMS sessions: once a day, 5 days per week, for 2 weeks, totaling 10 sessions. Additional treatment: inpatient conventional rehabilitation therapy, consisting of occupational and physical therapy for 30 minutes each, twice daily, for 2 weeks, as well as the routine pharmacotherapy based on the guidelines for management of patients with stroke.
Active Comparator: cTBS3; Absent responses in all ipsilateral corticospinal tract. continous Theta Burst Stimulation (cTBS) protocol of rTMS over contralateral primary motor cortex will be applied.	Device: cTBS3; rTMS intervention: 40 seconds of cTBS at 70% RMT, totaling 600 pulses. rTMS target: contralateral primary motor cortex. Total rTMS sessions: once a day, 5 days per week, for 2 weeks, totaling 10 sessions. Additional treatment: inpatient conventional rehabilitation therapy, consisting of occupational and physical therapy for 30 minutes each, twice daily, for 2 weeks, as well as the routine pharmacotherapy based on the guidelines for management of patients with stroke.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL)	Measurement for motor function of upper limb. Minimum: 0, Maximum: 66. Higher score means a better	From baseline T0 to Post-intervention T2 (2 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL)	Measurement for motor function of upper limb. Minimum: 0, Maximum: 66. Higher score means a better	From baseline T0 to During-intervention T1 (1 week)
Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL)	Measurement for motor function of upper limb. Minimum: 0, Maximum: 66. Higher score means a better	From baseline T0 to Follow-up T3 (2 months)
Differences of Fugl-Meyer Assessment score (FMA)	Measurement for motor function of all limbs. Minimum:0, Maximum: 100. Higher score means a better	From baseline T0 to During-intervention T1 (1 week)
Differences of Fugl-Meyer Assessment score (FMA)	Measurement for motor function of all limbs. Minimum:0, Maximum: 100. Higher score means a better	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Fugl-Meyer Assessment score (FMA)	Measurement for motor function of all limbs. Minimum:0, Maximum: 100. Higher score means a better	From baseline T0 to Follow-up T3 (2 months)
Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL)	Measurement for motor function of lower limb. Minimum:0, Maximum: 34. Higher score means a better	From baseline T0 to During-intervention T1 (1 week)
Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL)	Measurement for motor function of lower limb. Minimum:0, Maximum: 34. Higher score means a better	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL)	Measurement for motor function of lower limb. Minimum:0, Maximum: 34. Higher score means a better	From baseline T0 to Follow-up T3 (2 months)
Differences of Box and block test	Measurement for gross manual dexterity. Scored based on the number of blocks transferred from one compartment to the other compartment in 60 seconds.	From baseline T0 to During-intervention T1 (1 week)
Differences of Box and block test	Measurement for gross manual dexterity. Scored based on the number of blocks transferred from one compartment to the other compartment in 60 seconds.	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Box and block test	Measurement for gross manual dexterity. Scored based on the number of blocks transferred from one compartment to the other compartment in 60 seconds.	From baseline T0 to Follow-up T3 (2 months)
Differences of Functional Ambulation Category (FAC)	Measurement for gait function. Minimum: 0, Maximum: 5 Higher score means a better.	From baseline T0 to During-intervention T1 (1 week)
Differences of Functional Ambulation Category (FAC)	Measurement for gait function. Minimum: 0, Maximum: 5 Higher score means a better.	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Functional Ambulation Category (FAC)	Measurement for gait function. Minimum: 0, Maximum: 5. Higher score means a better.	From baseline T0 to Follow-up T3 (2 months)
Differences of Action Research Arm Test (ARAT)	Measurement to assess upper extremity performance (coordination, dexterity and functioning). Minimum: 0, Maximum: 57. Higher score means a better.	From baseline T0 to During-intervention T1 (1 week)
Differences of Action Research Arm Test (ARAT)	Measurement to assess upper extremity performance (coordination, dexterity and functioning). Minimum: 0, Maximum: 57. Higher score means a better.	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Action Research Arm Test (ARAT)	Measurement to assess upper extremity performance (coordination, dexterity and functioning). Minimum: 0, Maximum: 57. Higher score means a better.	From baseline T0 to Follow-up T3 (2 months)
Differences of Jebsen-Taylor hand function test	Measurement of fine and gross motor hand function using simulated activities of daily living. Total score is the sum of time taken for each sub-test, which are rounded to the nearest second. Shorter times indicate better performance.	From baseline T0 to During-intervention T1 (1 week)
Differences of Jebsen-Taylor hand function test	Measurement of fine and gross motor hand function using simulated activities of daily living. Total score is the sum of time taken for each sub-test, which are rounded to the nearest second. Shorter times indicate better performance.	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Jebsen-Taylor hand function test	Measurement of fine and gross motor hand function using simulated activities of daily living. Total score is the sum of time taken for each sub-test, which are rounded to the nearest second. Shorter times indicate better performance.	From baseline T0 to Follow-up T3 (2 months)
Differences of Hand grip strength test	Measurement of muscular strength or the maximum force generated by forearm muscles, measured by Jamar hydraulic hand dynamometer.	From baseline T0 to During-intervention T1 (1 week)
Differences of Hand grip strength test	Measurement of muscular strength or the maximum force generated by forearm muscles, measured by Jamar hydraulic hand dynamometer.	From baseline T0 to Post-intervention T2 (2 weeks)
Differences of Hand grip strength test	Measurement of muscular strength or the maximum force generated by forearm muscles, measured by Jamar hydraulic hand dynamometer.	From baseline T0 to Follow-up T3 (2 months)

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Seoul National University Hospital; National Research Foundation of Korea; Severance Hospital; Saint Vincent's Hospital, Korea; Bucheon St. Mary's Hospital; Ministry of Food and Drug Safety, Korea; Kumoh National Institute of Technology; NEUROPHET
• Investigators: Principal Investigator: Won Hyuk Chang, PhD, Samsung Medical Center

Publications and helpful links

General Publications

• Lee HS, Kim DH, Seo HG, Im S, Yoo YJ, Kim NY, Lee J, Kim D, Park HY, Yoon MJ, Kim YS, Kim H, Chang WH. Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study. Front Neurol. 2024 Jul 3;15:1427142. doi: 10.3389/fneur.2024.1427142. eCollection 2024.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: February 13, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Stroke; rTMS; Functional reserve
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: 2023-11-164

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No