Acute Ischemic Stroke
Conditions
Keywords
Acute Ischemic Stroke, EPCs, phase Ⅰ
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled, dose-Escalation clinical study to investigate the safety and efficacy of EPCs transplantation in Acute ischemic stroke.
Detailed description
Acute ischemic stroke (AIS) occurs when blood flow to the brain is blocked by a clot or mechanical event and is the most common type of stroke. However, due to the limitation of time and contraindications, only a few patients with AIS are eligible candidates. Endothelial progenitor cells (EPCs) have the potential to reduce brain damage from AIS. They can effectively repair endothelial cells with vascular injuries by directly differentiating into endothelial cells or releasing corresponding regulatory factors, which is a potentially important means for the prevention and treatment of a series of vascular system disorders. The introduction of induced pluripotent stem cells (iPSCs) technology provides a highly feasible option for clinical application of EPCs. Allogeneic iPSC-EPCs can be produced on a large scale to provide enough cells, fundamentally solving the problem of insufficient dosage, and making them a feasible clinical option for treatment of AIS.
Interventions
DRUGiEPCs
Patients receive iEPCs IV with the single dose
DRUGPlacebo
Patients receive placebo IV with a single dose
Sponsors
Linfen Central Hospital
Peking University Third Hospital
Xuanwu Hospital, Beijing
Beijing Tiantan Hospital
Linyi People's Hospital
Allife Medical Science and Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 1.Able to provide consent to study or consent is obtained from the patient's legal representative * 2.Male or females,aged 18 to 80 years * 3\. Subjects with acute ischemic stroke:1) Onset time ≤ 7 days; 2) Imaging confirmed infarction in the blood-supplying area of the internal carotid artery; 3) treated with thrombolysis and/or thrombolysis, or without the above treatment; * 4.Subjects with NIHSS score between≥6 points and≤24 points at the time of screening * 5.Eligible patients of childbearing potential(both men and women)if sexually active must agree to use a reliable method of contraception with their partners
Exclusion criteria
1. Impaired consciousness (NIHSS score Ia ≥ 2); 2. Disease progression or fluctuation in the subject after the first visit to the screening enrollment, which in the judgment of the investigator has a poor prognosis and will not benefit from this clinical study; 3. Those who have bleeding conversion as assessed by imaging after thrombolysis and/or thrombolysis; 4. History of previous intracranial hemorrhage (within 1 year), arteriovenous malformations, arterial entrapment, aneurysm (≥3 mm in maximum diameter), epilepsy, and history of brain tumor; 5. Abnormalities in major organ function 7\. severe respiratory disease that, as assessed by the investigator, may have an impact on the subject's determination of test results (active tuberculosis, chronic obstructive pulmonary disease, interstitial lung disease, severe or critical pneumonia); 8. Uncontrolled hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg) after treatment, which in the judgment of the investigator carries a high risk of bleeding and has a poor prognosis; 9. Those with malignant tumors or a history of malignant tumors; 10. Have an autoimmune disease or are undergoing immunotherapy; 11. Being pregnant or breastfeeding; 12. Allergic to multiple drugs (≥2) or allergic to human albumin; 13. have been alcohol- or drug-dependent in the 6 months prior to the onset of illness or have had an episode of acute alcoholism in the 24 h prior to the onset of illness or have had an episode of Those with acute alcohol intoxication within 24 h; 14. History of psychiatric illness or severe cognitive impairment that may affect the evaluation of neurologic function; 15. Positive for Hepatitis B surface antigen, positive for Hepatitis C virus antibody, positive for syphilis serum antibody or positive for HIV antibody; 16. Being enrolled in a clinical study of another drug; 17. Patients who, in the opinion of the investigator, are not suitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Incidence and severity of adverse events after iEPCs infusion | baseline to 1 year | Incidence and severity of adverse events assessed by CTCAE V5.0 during the twelve-month study period after iEPCs infusion. |
Other
| Measure | Time frame | Description |
|---|---|---|
| plasma HLA antibody | From enrollment to the end of treatment at 14 days, 1 month and 3 months | The change from the baseline of plasma HLA antibody will be calculated at Day 14，month 1, month 3 post infusion, as available. |
| plasma T lymphocytes | From enrollment to the end of treatment at 1 day , 3 days, 7 days, 14 days, 21 days, 1 month , 3 months, 6 months, 9 months, 12 months | The change from the baseline in plasma T lymphocytes will be calculated at day 1, day 3, day 7, day 14, day 21, month 1, month 3, month 6, month 9, month 12 post infusion, as available. |
| plasma iEPCs | From enrollment to the end of treatment at 30~40 mins, 1 day, 3 days, 7 days, 14 days, 21 days, 1 month, 2 months, 3 months | The change from the baseline in plasma iEPCs will be calculated at 30\ 40 min, day 1, day 3, day 7, day 14, day 21, month 1, month 2, month 3 post infusion, as available. |
| Modified Rankin Scale, mRS | From enrollment to the end of treatment at 1 month, 3 months, 6 months | The change from the baseline in mRS will be calculated at month 1, month 3, month 6, as available. The scale is divided into 7 degrees, from 0 (no deficit) to 6 (dead). |
| HLA matching | From enrollment to the end of treatment at 1 year | the level of HLA matching pairs of donor/recipient |
| activity of daily living, ADL | From enrollment to the end of treatment at 1 month, 3 months, 6 months | The change from the baseline in ADL will be calculated at month 1, month 3, month 6 post-treatment, as available. Every activity will be scored 5 and the range of scores is from 0 (normal) to 5. |
| cerebral infarct volume | From enrollment to the end of treatment at 7 days and 6 months | The change from baseline in cerebral infarct volume using MRI will be calculated at day 7, month 6 post-treatment, as available. |
| vascular endothelial growth factor, VEGF | From enrollment to the end of treatment at 1 day , 3 days, 7 days, 14 days, 21 days, 1 month , 3 months, 6 months, 9 months, 12 months | Changes of concentration of vascular endothelial growth factor（VEGF）in the serum from the baseline will be calculated at day 1, day 3, day 7, day 14, day 21, month 1, month 3, month 6, month 9, month 12 post-treatment, as available. |
| brain derived neurotrophic factor，BDNF | From enrollment to the end of treatment at 1 day , 3 days, 7 days, 14 days, 21 days, 1 month , 3 months, 6 months, 9 months, 12 months | Changes of concentration of brain derived neurotrophic factor (BDNF) in the serum from the baseline will be calculated at day 1, day 3, day 7, day 14, day 21, month 1, month 3, month 6, month 9, month 12 post-treatment, as available. |
| National Institute of Health stroke scale, NIHSS | From enrollment to the end of treatment at 1 month, 3 months, 6 months | The change from the baseline in NIHSS will be calculated at month 1, month 3, month 6 post-treatment, as available. The range of scores is from 0 (normal) to 42. |
Countries
China
Outcome results
None listed