Post-stroke cognitive impairment can limit rehabilitation, independence, and quality of life after ischemic stroke. This pilot randomized controlled trial evaluates whether mesenchymal stem cell-derived secretome, given in addition to standard stroke care and rehabilitation, improves cognitive recovery in patients with subacute ischemic stroke. Participants aged 40 to 75 years with ischemic stroke occurring 7 days to 3 months previously and mild-to-moderate cognitive impairment will be randomly assigned in a 1:1 ratio to receive standard care and rehabilitation plus MSC secretome or standard care and rehabilitation without MSC secretome. The primary outcome is the change in the Indonesian version of the Montreal Cognitive Assessment score. Secondary outcomes include quantitative electroencephalography parameters, serum brain-derived neurotrophic factor, serum interleukin-1β, NIHSS, modified Rankin Scale, and adverse events.
This study is a pilot, parallel-group, randomized controlled trial with blinded outcome assessment. The study population consists of patients aged 40 to 75 years with clinically and radiologically confirmed subacute ischemic stroke, defined as 7 days to 3 months after stroke onset. Eligible participants must be hemodynamically stable, able to undergo a basic neuropsychological assessment, and have mild-to-moderate cognitive impairment based on the Indonesian version of the Montreal Cognitive Assessment. Participants will be randomized in a 1:1 ratio using block randomization with allocation concealment. The intervention group will receive standard stroke care and rehabilitation plus umbilical cord mesenchymal stem cell-derived secretome. The control group will receive standard medical treatment and standardized stroke rehabilitation without MSC secretome. Outcome assessors will remain unaware of treatment allocation. Baseline assessments include demographic and vascular risk factor data, NIHSS, modified Rankin Scale, MoCA-Ina, quantitative electroencephalography, serum brain-derived neurotrophic factor, and serum interleukin-1β. Follow-up assessments will include cognitive, neurological, functional, electrophysiological, biomarker, and safety evaluations at the prespecified study visits. The primary outcome is the change in MoCA-Ina total score from baseline to week 8. Secondary outcomes include changes in delta-to-alpha ratio, delta-theta-to-alpha-beta ratio, relative alpha power, relative theta power, serum BDNF, serum IL-1β, NIHSS, modified Rankin Scale, and the incidence of adverse events. The primary analysis will follow the intention-to-treat principle, with per-protocol analysis as an additional analysis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
70
Umbilical cord mesenchymal stem cell-derived secretome is administered in addition to standard medical treatment and standardized stroke rehabilitation. The intervention is administered twice, on day 1 and day 8, according to the investigational product protocol. Participants are monitored during and after administration for hypersensitivity reactions, fever, and other adverse events.
Participants receive standard medical management for subacute ischemic stroke and standardized stroke rehabilitation according to the treating physician and institutional clinical practice. The same standard care and rehabilitation are provided to both study groups.
Hasanuddin University Hospital
Makassar, South Sulawesi, Indonesia
RECRUITINGChange in Montreal Cognitive Assessment-Indonesian Version Total Score
The MoCA-Ina assesses visuospatial-executive function, naming, attention, language, abstraction, delayed recall, and orientation. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. The outcome is the change in total MoCA-Ina score from baseline to the final follow-up assessment.
Time frame: Baseline to week 8
Change in Delta-to-Alpha Ratio on Quantitative Electroencephalography
The delta-to-alpha ratio is calculated from quantitative electroencephalography spectral power measurements. The outcome is the change in DAR from baseline to week 4 and week 8.
Time frame: Baseline, week 4, and week 8
Change in Delta-Theta-to-Alpha-Beta Ratio on Quantitative Electroencephalography
The delta-theta-to-alpha-beta ratio is calculated from quantitative electroencephalography spectral power measurements. The outcome is the change in DTABR from baseline to week 4 and week 8.
Time frame: Baseline, week 4, and week 8
Change in Relative Alpha Power on Quantitative Electroencephalography
Relative alpha power is derived from quantitative electroencephalography spectral power analysis. The outcome is the change in relative alpha power from baseline to week 4 and week 8.
Time frame: Baseline, week 4, and week 8
Change in Relative Theta Power on Quantitative Electroencephalography
Relative theta power is derived from quantitative electroencephalography spectral power analysis. The outcome is the change in relative theta power from baseline to week 4 and week 8.
Time frame: Baseline, week 4, and week 8
Change in Serum Brain-Derived Neurotrophic Factor Concentration
Serum brain-derived neurotrophic factor concentration is measured using an enzyme-linked immunosorbent assay. The outcome is the change in serum BDNF concentration from baseline to week 8.
Time frame: Baseline and week 8
Change in Serum Interleukin-1 Beta Concentration
Serum interleukin-1 beta concentration is measured using an enzyme-linked immunosorbent assay. The outcome is the change in serum IL-1 beta concentration from baseline to week 8.
Time frame: Baseline and week 8
Change in National Institutes of Health Stroke Scale Score
The National Institutes of Health Stroke Scale assesses neurological impairment. Scores range from 0 to 42, with higher scores indicating greater neurological impairment. The outcome is the change in NIHSS score from baseline to week 4 and week 8.
Time frame: Baseline, week 4, and week 8
Change in Modified Rankin Scale Score
The modified Rankin Scale assesses global disability after stroke. Scores range from 0 to 6, with higher scores indicating greater disability or death. The outcome is the change in modified Rankin Scale score from baseline to week 4 and week 8.
Time frame: Baseline, week 4, and week 8
Incidence of Treatment-Emergent Adverse Events
The number and proportion of participants experiencing adverse events, including hypersensitivity reactions, fever, administration-related reactions, hospitalization, seizure, infection, neurological deterioration, and death, will be recorded.
Time frame: From the first intervention through week 8
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