Exploratory Study of Intranasal Administration of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles for the Treatment of Ischemic Stroke

Official title

Exploratory Study of Intranasal Administration of Small Extracellular Vesicles Derived From Human Umbilical Cord Mesenchymal Stem Cells hUC-MSC-sEV-001 in the Treatment of Ischemic Stroke Patients

Overview

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

• Biological Intranasal 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,

Primary outcome measures

• Dose-Limiting Toxicity (DLT) Related to hUC-MSC-sEV-001 [Time frame: Day 14 (+-2) post-enrollment]

Secondary outcome measures (8)

• Serious adverse events related to the investigational drug within 90 (+-7) days [Time frame: At baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment]
• Distribution of Modified Rankin Scale (mRS) Scores within 90 (+-7) days [Time frame: baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment]
• Barthel Index within 90 (±7) days [Time frame: baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment]
• Five-level, five-dimensional EuroQol (EQ-5D-5L) [Time frame: baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment]
• Proportion of Modified Rankin Scale (mRS) Scores of 0-2 within 90 (+-7) days [Time frame: baseline, Day 7 (+-1), Day 14 (+-2), and Day 90 (+-7)post-enrollment]
• All-cause mortality at 90 (+-7) days [Time frame: Day 90 (+-7)post-enrollment]
• Changes in infarct volume at 14 (+-2) days compared to baseline [Time frame: baseline, Day 14 (+-2) post-enrollment]
• Change from Baseline in National Institutes of Health Stroke Scale (NIHSS) Score [Time frame: baseline, Day 7 (+-1) and Day 14 (+-2)post-enrollment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• 253 Gongye Blvd Middle, Guangzhou, Guangdong, China 510280 — Guangzhou

Identifiers

NCT: NCT07232563 · 2023-KY-343-04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗