Ischemic Stroke
Conditions
Keywords
Subacute Ischemic Stroke, Motor Recovery, Mesenchymal Stem Cell Secretome, Repetitive Transcranial Magnetic Stimulation, rTMS, Quantitative Electroencephalography, qEEG, Fugl-Meyer Motor Scale, Neuroplasticity
Brief summary
This randomized, double-blind, controlled clinical trial evaluates the effectiveness and safety of combined mesenchymal stem cell (MSC) secretome and repetitive transcranial magnetic stimulation (rTMS) for motor recovery in patients with subacute ischemic stroke. Participants will be randomized to either an intervention group receiving intravenous MSC secretome combined with high-frequency ipsilesional rTMS or a control group receiving placebo infusion and sham rTMS. The intervention is administered once weekly for 8 weeks. The primary outcome is change in motor function measured using the Fugl-Meyer Motor Scale. Secondary outcomes include changes in quantitative electroencephalography biomarkers, including sensorimotor rhythm, delta-theta-to-alpha-beta ratio, and beta coherence, as well as spasticity assessed using the Modified Ashworth Scale and treatment-related adverse events.
Detailed description
This study is a double-blind, randomized controlled clinical trial designed to evaluate the effectiveness and safety of combined intravenous mesenchymal stem cell (MSC) secretome and high-frequency repetitive transcranial magnetic stimulation (rTMS) in patients with subacute ischemic stroke. A total of 205 participants are planned to be enrolled. Eligible participants are patients aged 30 to 75 years with a first ischemic stroke confirmed by computed tomography or magnetic resonance imaging and who are able to undergo rTMS therapy. Participants will be randomized into an intervention group and a control group. The intervention group will receive intravenous MSC secretome at a dose of 1.5 × 10\^9 particle equivalents once weekly for 8 weeks, combined with high-frequency rTMS at 10 Hz, 1500 pulses per session, and an intensity of 80% of the resting motor threshold applied to the ipsilesional primary motor cortex (M1). The control group will receive a 0.9% sodium chloride placebo infusion and sham rTMS using procedures designed to resemble the active intervention. Motor function will be assessed using the Fugl-Meyer Motor Scale before and after the intervention. Quantitative electroencephalography will be used to evaluate neurophysiological biomarkers of neuroplasticity, including sensorimotor rhythm, delta-theta-to-alpha-beta ratio, and beta coherence. Spasticity will be assessed using the Modified Ashworth Scale. Safety will be evaluated by systematic monitoring and recording of adverse events throughout the intervention period. The primary objective is to compare the change in Fugl-Meyer Motor Scale scores between the intervention and control groups. Secondary objectives are to evaluate changes in quantitative electroencephalography parameters, assess treatment-related adverse events, and examine the relationship between clinical motor improvement and changes in neurophysiological biomarkers.
Interventions
BIOLOGICALMesenchymal Stem Cell-Derived Secretome
Intravenous mesenchymal stem cell-derived secretome at a dose of 1.5 × 10\^9 particle equivalents is administered once weekly for 8 weeks. Administration is performed through intravenous access using aseptic technique by trained medical personnel, with monitoring for possible adverse events during and after administration.
High-frequency repetitive transcranial magnetic stimulation is delivered at 10 Hz, 1500 pulses per session, at 80% of the resting motor threshold over the ipsilesional primary motor cortex (M1). Treatment is administered once weekly for 8 weeks.
Participants in the control group receive an intravenous infusion of 0.9% sodium chloride as placebo according to the same treatment schedule as the active secretome intervention.
DEVICESham Repetitive Transcranial Magnetic Stimulation
Sham repetitive transcranial magnetic stimulation is performed using procedures designed to resemble active rTMS without delivering therapeutic stimulation. Sham sessions follow the same treatment schedule as the active rTMS sessions.
Sponsors
Jumraini Tammasse
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants and outcome assessors are blinded to treatment allocation. The control group receives a placebo infusion and sham rTMS designed to resemble the active interventions.
Intervention model description
Participants are randomly assigned to two parallel groups. The intervention group receives intravenous mesenchymal stem cell secretome combined with high-frequency repetitive transcranial magnetic stimulation, while the control group receives placebo infusion and sham repetitive transcranial magnetic stimulation.
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 30 to 75 years. 2. Diagnosis of subacute ischemic stroke, 1 to 6 months after stroke onset. 3. First-ever ischemic stroke. 4. Ischemic stroke confirmed by magnetic resonance imaging (MRI) or computed tomography (CT). 5. Able to undergo repetitive transcranial magnetic stimulation (rTMS) therapy.
Exclusion criteria
1. History of active seizures. 2. Presence of intracranial metal or implanted devices that are contraindications to rTMS. 3. Severe systemic disease that may affect participant safety or interfere with study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fugl-Meyer Motor Scale Score | Baseline to week 8 | Motor function is assessed using the Fugl-Meyer Motor Scale. The motor score ranges from 0 to 100, with higher scores indicating better motor function and lower scores indicating greater motor impairment. The outcome is the change in total Fugl-Meyer Motor Scale score from baseline to the end of the 8-week intervention period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sensorimotor Rhythm on Quantitative Electroencephalography | Baseline to week 8 | Sensorimotor rhythm is assessed using quantitative electroencephalography as a neurophysiological marker of neuroplasticity. The outcome is the change in sensorimotor rhythm from baseline to the end of the 8-week intervention period. |
| Change in Delta-Theta-to-Alpha-Beta Ratio on Quantitative Electroencephalography | Baseline to week 8 | The delta-theta-to-alpha-beta ratio is derived from quantitative electroencephalography spectral analysis. The outcome is the change in delta-theta-to-alpha-beta ratio from baseline to the end of the 8-week intervention period. |
| Change in Beta-Band Coherence on Quantitative Electroencephalography | Baseline to week 8 | Beta-band coherence is assessed using quantitative electroencephalography as a measure of functional connectivity. The outcome is the change in beta-band coherence from baseline to the end of the 8-week intervention period. |
| Change in Modified Ashworth Scale Score | Baseline to week 8 | Spasticity is assessed using the Modified Ashworth Scale, which ranges from 0 to 4, with an additional grade of 1+. Higher scores indicate greater muscle tone and more severe spasticity, while lower scores indicate less spasticity. The outcome is the change in Modified Ashworth Scale score from baseline to the end of the 8-week intervention period. |
| Incidence of Adverse Events | Throughout the 8-week intervention period | The incidence and type of adverse events occurring during the intervention period will be recorded to evaluate treatment safety. |
Countries
Indonesia
Contacts
CONTACTJumraini Tammasse, Sp.N(K), Subsp.NRE(K)
CONTACTnovi tejaya, MD
PRINCIPAL_INVESTIGATORJumraini Tammasse, Sp.N, Subsp.NRE(K)
Hasanuddin University
Outcome results
None listed