Ischemic Stroke
Conditions
Keywords
ischemic stroke, stem cell, Extracellular Vesicles
Brief summary
Evaluation of the Safety and Preliminary Efficacy of Intranasal Administration of Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles (hUC-MSC-sEV-001) in Patients for Ischemic Stroke
Detailed description
Based on adhering to the GCP principles of national clinical trial research and the standardized processes of CROs, this study aims to evaluate the safety and preliminary efficacy of hUC-MSC-sEV-001 in treating ischemic stroke by recruiting a small sample population. Additionally, the study will seek to determine an appropriate dosage, laying the foundation for subsequent research.
Interventions
BIOLOGICALIntranasal Administration of Human Umbilical Cord Mesenchymal Stem Cell-Derived Small Extracellular Vesicles (hUC-MSC-sEV-001) Therapy
Experimental drug: hUC-MSC-SEV-001 nasal drops derived from small extracellular vesicles of human umbilical cord mesenchymal stem cells Treatment plan: On the basis of conventional treatment, hUC-MSC-SEV-001 nasal drops will be administered: hUC-MSC-SEV-001 will be administered via nasal drip for a total of 4 times, with a dosage of 1 × 10 \* 11articles per dose. The patient will receive one dose on the day of enrollment, and another dose of hUC-MSC-SEV-001 will be administered on the 2nd, 3rd, and 4th days after enrollment.
Sponsors
Zhujiang Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Ischemic Stroke * Age 18-70 years, no gender restriction * Confirmed anterior circulation occlusion by CTA or MR angiography (MRA) * Pre-stroke mRS score of 0-1 * Post-stroke ASPECTS score \>= 6 * Pre-enrollment NIHSS score\>= 6 * Within 24 hours to 14 days of stroke onset * Patients who have not received thrombolysis or endovascular treatment * No significant liver or kidney dysfunction: ALT and AST\<= 2.5 times the upper limit of normal, serum creatinine and blood urea nitrogen \<= 1.25 times the upper limit of normal * No significant cardiac dysfunction * The subject or legal representative can sign the informed consent form and comply with the requirements of the study for administration and follow-up.
Exclusion criteria
* Intracranial hemorrhagic conditions observed on cranial CT: hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, or hemorrhagic transformation, etc. * Known severe allergy to contrast agents (excluding mild rash-type allergies) * Known bleeding tendencies (including but not limited to): platelet count \< 100×10\^9/L; received heparin treatment within 48 hours with aPTT \>= 35s; currently taking warfarin with INR \> 1.7 * Patients with brain tumors, or a history of epilepsy and severe head trauma * Patients with other systemic malignancies * Patients with other serious systemic diseases such as immunodeficiency, coagulation disorders, etc. * Patients with Alzheimer's disease, Parkinson's disease, or other neurodegenerative diseases that prevent them from completing follow-up * Patients with severe local infection, systemic infection, immunodeficiency, or those currently taking immunosuppressants * Patients who are positive for hepatitis B surface antigen or currently suffering from other infectious diseases * Patients who have allergic reactions to the drug used in this study or similar drugs * Patients with known allergic constitution * Patients with nasal structural abnormalities or lesions * Patients with cerebrospinal fluid rhinorrhea * Patients who have participated in other clinical trials within the past 3 months * Unwilling or unable to comply with the procedures specified in the protocol * Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use appropriate contraceptive measures * Patients clearly lacking the compliance to complete the clinical trial, such as those suffering from uncontrolled mental illness * Other situations deemed unsuitable for enrollment by the researchers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Limiting Toxicity (DLT) Related to hUC-MSC-sEV-001 | Day 14 (+-2) post-enrollment | Dose-Limiting Toxicity (DLT) Related to hUC-MSC-sEV-001 Includes: 1. Grade 3-4 severe adverse events occurring on day 14 (+-2), graded according to Common Terminology Criteria for Adverse Events （CTCAE） V5.0; 2. NIHSS score increase of ≥4 from baseline on day 14 (+-2); NIHSS score assessed by a professional rehabilitation physician; 3. Symptomatic intracranial hemorrhage occurring on day 14 (+-2); detected via CT scan and patient symptom presentation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Modified Rankin Scale (mRS) Scores within 90 (+-7) days | baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment | Measured using the Modified Rankin Scale (mRS) scale. The mRS ranges from 0 to 6, with higher numbers indicating greater disability. |
| Barthel Index within 90 (±7) days | baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment | Measured using the Barthel Index. The total score of the Barthel Index ranges from 0 to 100 points. A higher Barthel Index score indicates a better (more positive) outcome, while a lower score indicates a poorer (more challenging) outcome. |
| Five-level, five-dimensional EuroQol (EQ-5D-5L) | baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment | Measured using the Five-level, five-dimensional EuroQol (EQ-5D-5L). It has two main scores with distinct ranges. The Index Score (Utility Score) comes from mapping responses on 5 health dimensions to a standardized scale. Its minimum is typically -0.594 to -0.101 (varies by region; negatives mean health worse than death for some), and maximum is 1.0 (full health, no limitations). The Visual Analog Scale (VAS) Score is a subjective self-rating on a 100mm vertical line, with 0 (Worst imaginable health) as minimum and 100 (Best imaginable health) as maximum. For both scores, higher means better HRQoL. |
| Serious adverse events related to the investigational drug within 90 (+-7) days | At baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment | The occurrence of serious adverse events related to the investigational drug will be assessed according to CTCAE v5.0, based on monitoring of the patient's vital signs (pulse, blood pressure, respiration, and body temperature), as well as laboratory tests including complete blood count, urinalysis, liver and kidney function, glucose and lipid metabolism, coagulation profile, serum electrolytes, tumor markers, and electrocardiogram. |
| All-cause mortality at 90 (+-7) days | Day 90 (+-7)post-enrollment | Contact the patient or their family to confirm survival status |
| Changes in infarct volume at 14 (+-2) days compared to baseline | baseline, Day 14 (+-2) post-enrollment | Using CTA、 CTP and MRI to measure changes in infarct volume in patients |
| Change from Baseline in National Institutes of Health Stroke Scale (NIHSS) Score | baseline, Day 7 (+-1) and Day 14 (+-2)post-enrollment | Measured using the National Institutes of Health Stroke Scale (NIHSS). Its total score range spans from a minimum of 0 points (indicating no detectable neurological deficits, suggesting minimal or no stroke-related impairment) to a maximum of 42 points (representing severe, widespread neurological dysfunction, often associated with profound stroke-related disability); regarding the scoring standard, a higher score means a worse outcome. |
| Proportion of Modified Rankin Scale (mRS) Scores of 0-2 within 90 (+-7) days | baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment | Measured using the mRS scale |
Countries
China
Contacts
Primary ContactRun Zhang, Philosophy Doctor
Outcome results
None listed