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

NCT ID: NCT06270238

Last Updated: 2024-02-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-13

Study Completion Date

2025-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

prospective, single-blind with blind observer, parallel-group design, multi-center, randomized controlled clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
The participants, assessors, and investigators will be blinded, not be aware of the group allocation. Statistical analysis will also be conducted by data analysts without awareness of the group allocation. Only clinicians applying rTMS intervention will not be blinded, as they will apply rTMS over different stimulation sites based on the protocols. Blinding will be continued until the end of the study, including data analysis.

Study Groups

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High-Frequency1

Confirmed responses in TMS-induced MEP: Preserved ipsilateral corticospinal tract.

High-frequency rTMS over ipsilateral primary motor cortex will be applied.

Group Type EXPERIMENTAL

High-Frequency1

Intervention Type DEVICE

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.

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.

Group Type ACTIVE_COMPARATOR

cTBS1

Intervention Type DEVICE

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.

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.

Group Type EXPERIMENTAL

High-Frequency2

Intervention Type DEVICE

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.

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.

Group Type ACTIVE_COMPARATOR

cTBS2

Intervention Type DEVICE

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.

High-Frequency3

Absent responses in all ipsilateral corticospinal tract.

High-frequency rTMS over contralateral primary motor cortex will be applied.

Group Type EXPERIMENTAL

High-Frequency3

Intervention Type DEVICE

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.

cTBS3

Absent responses in all ipsilateral corticospinal tract.

continous Theta Burst Stimulation (cTBS) protocol of rTMS over contralateral primary motor cortex will be applied.

Group Type ACTIVE_COMPARATOR

cTBS3

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Research Foundation of Korea

OTHER

Sponsor Role collaborator

Ministry of Food and Drug Safety, Korea

OTHER_GOV

Sponsor Role collaborator

Seoul National University Hospital

OTHER

Sponsor Role collaborator

Bucheon St. Mary's Hospital

OTHER

Sponsor Role collaborator

Saint Vincent's Hospital, Korea

OTHER

Sponsor Role collaborator

Severance Hospital

OTHER

Sponsor Role collaborator

Kumoh National Institute of Technology

UNKNOWN

Sponsor Role collaborator

NEUROPHET

INDUSTRY

Sponsor Role collaborator

Samsung Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Won Hyuk Chang

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Won Hyuk Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

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Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Countries

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South Korea

Central Contacts

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Won Hyuk Chang, PhD

Role: CONTACT

82-2-3410-6068

Ho Seok Lee, PhD

Role: CONTACT

82-2-3410-2810

Facility Contacts

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Won Hyuk Chang, PhD

Role: primary

+82-2-3410-6068

References

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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.

Reference Type DERIVED
PMID: 39022726 (View on PubMed)

Other Identifiers

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2023-11-164

Identifier Type: -

Identifier Source: org_study_id

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