MSC Secretome Therapy for Cognitive Recovery After Subacute Ischemic Stroke

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.

Inclusion criteria

• Age 40 to 75 years.
• Diagnosis of ischemic stroke confirmed by clinical examination and computed tomography or magnetic resonance imaging.
• Stroke onset between 7 days and 3 months before enrollment.
• Hemodynamically stable.
• Able to undergo a basic neuropsychological assessment.
• Mild-to-moderate cognitive impairment based on the Indonesian version of the Montreal Cognitive Assessment.
• Willing to participate in the study and provide written informed consent.

Exclusion criteria

• Hemorrhagic stroke or mixed ischemic and hemorrhagic stroke.
• Severe aphasia, impaired consciousness, or severe sensory deficits that make cognitive assessment invalid.
• History of dementia before stroke or a major neurodegenerative disorder.
• Active infection, active autoimmune disease, active malignancy, severe renal failure, or severe liver failure.
• Uncontrolled epilepsy.
• Concurrent participation in another clinical trial.
• Contraindication to any study intervention or study procedure.