Stroke, Ischemic
Conditions
Keywords
Stroke, Mesenchymal stem cells, Stem cells, Neurogenesis
Brief summary
The objectives of this study was to test hypothesis that ischemic stroke patients having moderate to severe persistent neurologic deficit will have better outcomes with intravenous transplantation of autologous mesenchymal stem cells (MSCs) expanded with autologous serum that is obtained at acute phase of stroke than patients receiving standard treatment.
Detailed description
In this study, we will use autologous 'ischemic' serum that obtained at the earliest time point as possible (immediate after randomization) for the purpose of ischemic preconditioning. We have recently conducted preclinical studies on the effects of ischemic preconditioning on the MSC functions. We have evaluated the characteristics of rat MSCs after culture with fetal bovine serum (FBS) or serum obtained from rat stroke model. Compared to FBS, the use of serum obtained from rat stroke model resulted in more rapid expansion of MSCs, which reduces cell preparation time by increase in G2/M phase, decreased cell death/senescence, increased trophic factor secretion, and increased migration capacity.
Interventions
OTHERMesenchymal stem cell
intravenous transplantation of autologous mesenchymal stem cells expanded with autologous serum
Sponsors
Pharmicell Co., Ltd.
Samsung Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Men or women (women must be of non-child bearing potential), age 30-75 yrs. 2. Have a stroke that is observed within 90 days of the onset of symptoms 3. Radiologically 1. Relevant lesions within the middle cerebral artery territory (MCA) as assessed using diffusion-weighted imaging (DWI). 2. The maximum diameter of the stroke region in any dimension must be ≥15 mm. 3. Not involving more than a half of the ipsilateral periventricular zone 4. Clinically (National Institutes of Health stroke scale, NIHSS) 1. Moderate-to severe persistent neurologic deficit (NIHSS of 6-21 inclusive) 2. New onset of extremity paresis on the affected side, defined as a score of 2-4 on the NIHSS Motor Arm (item 5) or Leg (item 6) question. 3. Must be alert or drowsy but easily arousable as defined by score of 0-1 on the NIHSS Level of Consciousness question (item 1). 4. Slow recovery defined as Change in NIHSS ≤1 point/3 days 5. Willingness 1. Reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy as indicated for the post stroke deficits. 2. Able to participate in the evaluation process to the point of accurate assessment. 3. Willing and able to comply with scheduled visits, lifestyle guidelines, treatment plan, laboratory tests, and other study procedures. 4. Evidence of a personally signed and dated informed consent document.
Exclusion criteria
1. Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke modified Rankin score of 2 or more. 2. Have a stroke that is either 1. lacunar infarction 2. Hematologic cause of stroke 3. Recurrent or progressive stroke within 1 week at the time of screening. 3. Hematologic disorders or bone marrow suppression. 4. Have a severe medical illness 1. Severe heart failure 2. Severe febrile illness 3. Hepatic or renal dysfunction 4. Active cancer 5. Any evidence of chronic co-morbid condition or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject's survival or limit ability to complete the study. 5. Presence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis on admission blood tests 6. Presence of depression that is active and not adequately controlled such that it interfere with major activities of daily living immediately prior to the current stroke. 7. Presence of dementia prior to the current stroke that is likely to confound clinical evaluation. 8. Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test or lactating females. 9. Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol 10. Subjects unwilling to undergo bone marrow aspiration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Categorical shift in modified Rankin scale (mRS) | 90 days after the cell treatment | Categorical shift in mRS at 90 days after the cell treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of National Institutes of Health stroke scale (NIHSS) | 90 days after the cell treatment | Change of NIHSS between pre- and post-treatment 90 days |
| Early improvement of National Institutes of Health stroke scale (NIHSS) | 14 days after the cell treatment | ≥5 points improvement or score of 0-2 on NIHSS score at 14 days after treatment |
| Dichotomized modified Rankin scale (mRS) | 90 days after the cell treatment | mRS ≤2 at 90 days after treatment |
| Change of modified Rankin scale (mRS) | 90 days after the cell treatment | Change of mRS between pre- and post-treatment 90 days |
| Dichotomized modified Barthel index (mBI) | 90 days after the cell treatment | mBI ≥60 at 90 days after treatment |
| Change of modified Barthel index (mBI) | 90 days after the cell treatment | Change of mBI between pre- and post-treatment 90 days |
| Change of Fine motor function | 90 days after the cell treatment | Change of Fine motor function (Purdue Pegboard test and Box and block test) between pre- and post-treatment 90 days |
| Change of Mobility | 90 days after the cell treatment | Change of Mobility (Functional ambulatory category and 10m-Gait speed) between pre- and post-treatment 90 days |
| Change of mini-mental status exam (MMSE) | 90 days after the cell treatment | Change of MMSE between pre- and post-treatment 90 days |
| Change of quality of life | 90 days after the cell treatment | Change of EuroQol 5d (EQ-5D) between pre- and post-treatment 90 days |
| Safety outcome | During 90 days after the cell treatment | 1. Death: All causes of death 2. Recurrence: Recurrent stroke or transient ischemic attack 3. The immediate reaction: Allergic reactions (tachycardia, fever, skin eruption, leukocytosis) Local complications (hematoma or local infection at the site of bone marrow aspiration) Vascular obstruction (tachypnea, oliguria, or peripheral vascular insufficiency) Systemic complications (infections,laboratory findings). 4. Long-term adverse effects possibly related to MSC treatment Tumor formation (physical examination, plain x-ray, f/u MRI at 90 days after treatment), Aberrant connections (newly diagnosed seizure or arrhythmia) |
| Change of gross motor function | 90 days after the cell treatment | Change of Gross motor function (Motricity index and Fugl-Meyer assessment)between pre- and post-treatment 90 days |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploration of biomarkers | During 90 days after the cell treatment | SDF(stromal cell-derived factor)-1ɑ (chemokine) S100ß (protection and regeneration) HIF(Hypoxia-inducible factor)-1 (preconditioning) Circulating MSCs and MSC-derived microparticles (CD105-CXCR4(C-X-C chemokine receptor type 4)-PS(phosphoserine)) BDNF (Brain-derived neurotrophic factor) levels and it's polymorphism, and VEGF (Vascular endothelial growth factor) levels Resting-state functional MRI & Diffusion tensor imaging |
Countries
South Korea
Contacts
Primary ContactOh Young Bang, MD
Backup ContactSang Ae Park, RN
Outcome results
None listed