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

Official title

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

Overview

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

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.

Interventions

• 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 pharma
• 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.
• 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 guidelin
• 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.
• 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 g
• 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.

Primary outcome measures

• Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL) [Time frame: From baseline T0 to Post-intervention T2 (2 weeks)]

Secondary outcome measures (12)

• Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL) [Time frame: From baseline T0 to During-intervention T1 (1 week)]
• Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL) [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Fugl-Meyer Assessment score (FMA) [Time frame: From baseline T0 to During-intervention T1 (1 week)]
• Differences of Fugl-Meyer Assessment score (FMA) [Time frame: From baseline T0 to Post-intervention T2 (2 weeks)]
• Differences of Fugl-Meyer Assessment score (FMA) [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL) [Time frame: From baseline T0 to During-intervention T1 (1 week)]
• Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL) [Time frame: From baseline T0 to Post-intervention T2 (2 weeks)]
• Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL) [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Box and block test [Time frame: From baseline T0 to During-intervention T1 (1 week)]
• Differences of Box and block test [Time frame: From baseline T0 to Post-intervention T2 (2 weeks)]
• Differences of Box and block test [Time frame: From baseline T0 to Follow-up T3 (2 months)]
• Differences of Functional Ambulation Category (FAC) [Time frame: From baseline T0 to During-intervention T1 (1 week)]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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

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

Triple blind

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center — Seoul

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. PMID 39022726

Identifiers

NCT: NCT06270238 · 2023-11-164

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗