A Phase IIa Randomized, Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Intravenous Infusion of Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) in the Treatment of Acute Ischemic Stroke (AIS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- The proportion of subjects with an mRS score of 0-2 at different follow-up visits after treatment.
研究概览
简要总结
This is a Phase IIa clinical trial with a three-arm design that utilizes randomization, double-blinding, and placebo control. The primary objective of this study is to evaluate the efficacy of single and multiple intravenous infusions of hUC-MSCs injection in patients with AIS. The secondary objective is to assess the safety and tolerability of single and multiple intravenous infusions of hUC-MSCs injection in patients with AIS. The exploratory objective is to investigate the pharmacokinetic and pharmacodynamic characteristics of hUC-MSCs injection in patients with AIS.
详细描述
Stroke is a disease with high incidence, disability rate, and mortality rate, ranking as the second leading cause of death globally and the leading cause in China. Acute ischemic stroke (AIS) accounts for approximately 60%-80% of all strokes. The most effective treatments for AIS are revascularization therapies within the time window, including intravenous thrombolysis with tissue plasminogen activator (t-PA) and mechanical thrombectomy. Although t-PA thrombolysis is effective, it can cause reperfusion injury, exacerbating a series of inflammatory damages. Additionally, the success rate of thrombolysis and thrombectomy is closely related to the onset time. The time window within 4.5 hours or 6 hours is considered effective for rescuing the ischemic penumbra, and only a minority of AIS patients can receive thrombolytic therapy. Some patients have contraindications to thrombolysis, and endovascular treatment is only suitable for large vessel occlusion. Furthermore, in China, low public awareness of early disease recognition, insufficient prehospital emergency capabilities, in-hospital emergency delays, and other factors lead to delayed AIS treatment and a low thrombolysis rate.
Studies have shown that mesenchymal stem cells can reduce the infarct area and alleviate blood-brain barrier damage by regulating the microenvironment of damaged brain tissue, alleviating inflammatory responses, and promoting angiogenesis, neurogenesis, and neurovascular repair. This study aims to evaluate the efficacy, safety, and tolerance of single and multiple intravenous infusions of hUC-MSCs injection in the treatment of AIS patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 75 years, inclusive, regardless of gender.
- •Diagnosis of acute ischemic stroke (AIS).
- •Onset time ≤ 72 hours.
- •Anterior circulation cerebral infarction.
- •Modified Rankin Scale (mRS) score ≤ 1 before the onset of this stroke.
- •National Institutes of Health Stroke Scale (NIHSS) score between 8 and 20 (inclusive) at screening, and NIHSS item 1a (level of consciousness) score ≤
- •The subject or their legal guardian has signed the informed consent form.
排除标准
- •Planned or already undergone thrombolysis or thrombectomy for this stroke.
- •History of epilepsy (excluding secondary epilepsy that does not currently require medication), Parkinson's disease, Alzheimer's disease, severe depression, or other diseases that the investigator deems would affect the subject's participation in the trial or the assessment of efficacy.
- •Presence of intracranial hemorrhagic disease (e.g., intracerebral hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma, etc.). If only petechial bleeding is present, the investigator may determine whether the subject is suitable for inclusion in the study.
- •Computed tomography (CT) or magnetic resonance imaging (MRI) of the head showing a large ischemic area in the middle cerebral artery territory or midline shift greater than 1 cm on head CT/MRI, and the investigator assesses a high likelihood of surgical intervention or poor prognosis.
- •Presence of brain tumor or history of malignancy.
- •Liver or kidney insufficiency during the screening period: Aspartate aminotransferase (AST) > 2.5 × upper limit of normal, alanine aminotransferase (ALT) > 2.5 × upper limit of normal, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m².
- •History of severe cardiovascular disease, which the investigator deems unsuitable for participation in this clinical trial.
- •Severe infection, including sepsis, septic shock, severe pneumonia, etc.
- •Systemic corticosteroid ( > 10 mg/day prednisone equivalent) or immunosuppressive drug treatment within 14 days before receiving the investigational drug or during the trial.
- •History of alcohol abuse within the past year (defined as an average of more than 2 units per day (1 unit = 10 mL ethanol, i.e., 1 unit = 200 mL of 5% alcohol beer or 25 mL of 40% alcohol spirits or 85 mL of 12% alcohol wine).
- •Pregnant or breastfeeding women; or unwillingness to use reliable contraception (e.g., condoms) throughout the study period, or plans to donate sperm or eggs, or have plans for pregnancy.
- •Participation in an interventional clinical trial within the past 3 months, or receipt of other cell therapy (excluding blood transfusion).
- •Other situations in which the investigator deems the patient unsuitable for participation in this study (including but not limited to non-compliance with the principle of patient benefit, poor patient compliance, unacceptable laboratory abnormalities, etc.).
研究组 & 干预措施
Group 2
Subjects receive three infusions of hUC-MSCs.
干预措施: hUC-MSCs treatment (low dose) (Drug)
Group 1
Subjects receive one infusion of hUC-MSCs infusions.
干预措施: hUC-MSCs treatment (high dose) (Drug)
Placebo Control Group
Subjects receive three infusions of cell medium placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
The proportion of subjects with an mRS score of 0-2 at different follow-up visits after treatment.
时间窗: 360 days
Evaluate each patient's modified Rankin Scale (mRS) score, with a total score ranging from 0 to 6, where a higher score indicates a poorer outcome. Determine the proportion of patients with an mRS score of 0-2 at different follow-ups after treatment.
The proportion of subjects with an NIHSS improvement of ≥4 points at different follow-up visits after treatment
时间窗: 90 days
Evaluate each patient's National Institutes of Health Stroke Scale (NIHSS) score at different follow-up time points after treatment. The NIHSS score ranges from 0 to 42, with higher scores indicating more severe neurological impairment. Determine the proportion of subjects with an improvement of ≥4 points in their NIHSS score.
Changes in NIHSS score from baseline at different follow-up visits after treatment
时间窗: 90 days
Evaluate each patient's National Institutes of Health Stroke Scale (NIHSS) score before treatment and at different follow-up time points after treatment. The NIHSS score ranges from 0 to 42, with higher scores indicating more severe neurological impairment. Determine the changes in NIHSS scores relative to the baseline.
Trends in the distribution of mRS scores (0-6) at different follow-up visits after treatment
时间窗: 360 days
Evaluate the modified Rankin Scale (mRS) score for each patient, with a total score ranging from 0 to 6, where a higher score indicates a poorer outcome. Determine the distribution trend of mRS scores (0-6) at different follow-up visits after treatment.
The proportion of subjects with a Barthel Index (BI) score of ≥95 at different follow-up visits after treatment
时间窗: 360 days
Evaluate the Barthel Index of Activities of Daily Living (BI) score for each patient, which ranges from 0 to 100, with higher scores indicating better independence and less dependence of the patient. Determine the proportion of subjects with a BI score of ≥95 at different follow-up visits after treatment.
Changes in Fugl-Meyer Motor Function Assessment Scale score from baseline at different follow-up visits after treatment
时间窗: 360 days
Evaluate the Fugl-Meyer Motor Function Assessment Scale score for each patient before and after treatment. The scale consists of 50 items, with a maximum total score of 100, where a higher score indicates a better outcome. Determine the change in Fugl-Meyer Motor Function Assessment Scale score from baseline at different follow-up visits after treatment.
次要结局
- Adverse Events(360 days)
- All-cause mortality rate(360 days)