Stroke
Conditions
Keywords
Stroke, rTMS, Functional reserve
Brief summary
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
DEVICEHigh-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.
DEVICEcTBS1
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.
DEVICEHigh-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.
DEVICEcTBS2
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.
DEVICEHigh-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.
DEVICEcTBS3
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.
Sponsors
Samsung Medical Center
National Research Foundation of Korea
Ministry of Food and Drug Safety, Korea
Seoul National University Hospital
Bucheon St. Mary's Hospital
Saint Vincent's Hospital, Korea
Severance Hospital
Kumoh National Institute of Technology
NEUROPHET
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
prospective, single-blind with blind observer, parallel-group design, multi-center, randomized controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL) | From baseline T0 to Post-intervention T2 (2 weeks) | Measurement for motor function of upper limb. Minimum: 0, Maximum: 66. Higher score means a better |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Differences of Fugl-Meyer Assessment score of Upper Extremity (FMA-UL) | From baseline T0 to During-intervention T1 (1 week) | Measurement for motor function of upper limb. Minimum: 0, Maximum: 66. Higher score means a better |
| Differences of Fugl-Meyer Assessment score (FMA) | From baseline T0 to During-intervention T1 (1 week) | Measurement for motor function of all limbs. Minimum:0, Maximum: 100. Higher score means a better |
| Differences of Fugl-Meyer Assessment score of Lower Extremity (FMA-LL) | From baseline T0 to During-intervention T1 (1 week) | Measurement for motor function of lower limb. Minimum:0, Maximum: 34. Higher score means a better |
| Differences of Box and block test | From baseline T0 to During-intervention T1 (1 week) | Measurement for gross manual dexterity. Scored based on the number of blocks transferred from one compartment to the other compartment in 60 seconds. |
| Differences of Functional Ambulation Category (FAC) | From baseline T0 to During-intervention T1 (1 week) | Measurement for gait function. Minimum: 0, Maximum: 5 Higher score means a better. |
| Differences of Action Research Arm Test (ARAT) | From baseline T0 to During-intervention T1 (1 week) | Measurement to assess upper extremity performance (coordination, dexterity and functioning). Minimum: 0, Maximum: 57. Higher score means a better. |
| Differences of Jebsen-Taylor hand function test | From baseline T0 to During-intervention T1 (1 week) | 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. |
| Differences of Hand grip strength test | From baseline T0 to During-intervention T1 (1 week) | Measurement of muscular strength or the maximum force generated by forearm muscles, measured by Jamar hydraulic hand dynamometer. |
Countries
South Korea
Contacts
CONTACTWon Hyuk Chang, PhD
CONTACTHo Seok Lee, PhD
PRINCIPAL_INVESTIGATORWon Hyuk Chang, PhD
Samsung Medical Center
Outcome results
None listed