Ischemic Stroke, Post-Stroke Cognitive Impairment
Conditions
Keywords
Subacute ischemic stroke, Post-stroke cognitive impairment, Mesenchymal stem cell secretome, MSC secretome, Cognitive recovery, MoCA-Ina, Quantitative electroencephalography, qEEG, Brain-derived neurotrophic factor, BDNF, Interleukin-1 beta, IL-1β
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALUmbilical Cord Mesenchymal Stem Cell-Derived Secretome
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.
OTHERStandard Stroke Care and Rehabilitation
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.
Sponsors
Jumraini Tammasse
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors responsible for the MoCA-Ina, NIHSS, modified Rankin Scale, and quantitative electroencephalography assessments are blinded to treatment allocation. The randomization sequence and treatment assignment are not disclosed to the outcome assessors
Intervention model description
Participants are randomly assigned in a 1:1 ratio to two parallel groups. The experimental group receives umbilical cord mesenchymal stem cell-derived secretome in addition to standard stroke care and rehabilitation. The control group receives standard stroke care and rehabilitation without MSC secretome.
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 40 to 75 years. 2. Diagnosis of ischemic stroke confirmed by clinical examination and computed tomography or magnetic resonance imaging. 3. Stroke onset between 7 days and 3 months before enrollment. 4. Hemodynamically stable. 5. Able to undergo a basic neuropsychological assessment. 6. Mild-to-moderate cognitive impairment based on the Indonesian version of the Montreal Cognitive Assessment. 7. Willing to participate in the study and provide written informed consent.
Exclusion criteria
1. Hemorrhagic stroke or mixed ischemic and hemorrhagic stroke. 2. Severe aphasia, impaired consciousness, or severe sensory deficits that make cognitive assessment invalid. 3. History of dementia before stroke or a major neurodegenerative disorder. 4. Active infection, active autoimmune disease, active malignancy, severe renal failure, or severe liver failure. 5. Uncontrolled epilepsy. 6. Concurrent participation in another clinical trial. 7. Contraindication to any study intervention or study procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montreal Cognitive Assessment-Indonesian Version Total Score | Baseline to week 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Delta-to-Alpha Ratio on Quantitative Electroencephalography | Baseline, week 4, and week 8 | 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. |
| Change in Delta-Theta-to-Alpha-Beta Ratio on Quantitative Electroencephalography | Baseline, week 4, and week 8 | 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. |
| Change in Relative Alpha Power on Quantitative Electroencephalography | Baseline, week 4, and week 8 | 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. |
| Change in Relative Theta Power on Quantitative Electroencephalography | Baseline, week 4, and week 8 | 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. |
| Change in Serum Brain-Derived Neurotrophic Factor Concentration | Baseline and week 8 | 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. |
| Change in Serum Interleukin-1 Beta Concentration | Baseline and week 8 | 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. |
| Change in National Institutes of Health Stroke Scale Score | Baseline, week 4, and week 8 | 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. |
| Change in Modified Rankin Scale Score | Baseline, week 4, and week 8 | 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. |
| Incidence of Treatment-Emergent Adverse Events | From the first intervention through week 8 | 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. |
Countries
Indonesia
Contacts
CONTACTJumraini Tammasse, Sp.N, Subsp.NRE(K)
PRINCIPAL_INVESTIGATORJumraini Tammasse, Sp.N, Subsp.NRE(K)
Hasanuddin University
Outcome results
None listed