An Exploratory Study on the Use of Intrathecal Injection of Human Autologous Mesenchymal Stromal Cells Derived Extracellular Vesicles for the Treatment of Syringomyelia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of participants who experienced dose-limiting Toxicities (DLTs)
研究概览
简要总结
This is a open-label, single-arm, dose escalation phase I clinical trial. The goal of this clinical trial is to evaluate the safety and preliminary efficacy of Intrathecal injection human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (hUC-MSC-sEV) in syringomyelia.
详细描述
This is a open-label, single-arm, dose escalation phase I clinical trial. The study will consist of one part: Part 1 will be a dose-escalation study.
A traditional 3+3 dose-escalation design will be implemented in Part 1. Cohort 1 will receive low-dose1×1011particles; Cohort 2 will receive middle-dose2×1011particles; and Cohort 3 will receive high-dose3×1011particles. (Cohort 1 to Cohort 3 will receive a dose of 2 ml per lumbar puncture, administered once a month, for a total of three months.) If no dose-limiting toxicities (DLTs) are observed for 2 weeks after the administration of the first Intrathecal injection, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in one participant in the cohort, an additional three participants will be treated at the same dose level. Dose escalation will be stopped if DLTs are observed in more than 33% of the participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients whose MR revealed that syrinx have shrunk after surgery for a year but whose clinical spinal cord symptoms have not improved.
- •Patients whose MR revealed that syrinx spontaneously resolution under conservative observation, but whose clinical spinal cord symptoms have not improved.
- •Age: 18-70 years, inclusion of both genders;
排除标准
- •1. Those with diabetes, heart disease, or impaired liver or kidney function;
- •Those with other diseases such as brainstem tumors and spinal cord tumors;
- •Infected individuals with lumbar puncture sites;
- •Those with previous or detected abnormalities in the heart;
- •Those who have autoimmune diseases and need to be treated with immunosuppressants;
- •Those who are allergic to the research drugs;
- •Have participated in other interventional clinical studies or received other cell therapies (excluding blood transfusion) within the past three months;
- •Those who are unconscious, unable to express subjective discomfort symptoms and unable to cooperate with neurological function tests, those who have been receiving drug treatment for a long time and do not cooperate with the treatment plan;
- •Pregnant women, women who are breastfeeding and those planning to become pregnant;
- •Serological tests (HBsAg, anti-HCV, anti-HIV, TP-Ab) are positive;
- •Other circumstances where the researcher deems the patient unsuitable to participate in this study (including but not limited to not meeting the treatment that benefits the patient the most, poor patient compliance, abnormal laboratory test indicators that cannot be accepted, etc.).
- •Rejection Criteria:
- •misdiagnosis; use of any medication that may significantly impact the assessment accuracy of hUC-MSC-sEV engraftment; absence of any evaluation outcome at any time point during the follow-up period
- •Cessation Criteria:
- •individual wishes of the subjects; occurrence of any hUC-MSC-sEV-associated serious adverse event (SAE) that may aggravate neurological dysfunction, or require prolongation of existing hospitalization, or need hospital readmission, or impair consciousness, or be life-threatening, or even lead to death in any subject; detection of any major mistake in the present protocol during the implementation of this clinical trial; the national administration agency requires the clinical trial to be halted
研究组 & 干预措施
Exosomes group
Patients in this arm will receive exosomes derived from human umbilical cord blood mesenchymal stem cells as a Intrathecal injection, administered once a month, for a total of three months.
干预措施: Exosomes group (Drug)
结局指标
主要结局
Number of participants who experienced dose-limiting Toxicities (DLTs)
时间窗: 24 hours, 4±1 Weeks, 8±1 Weeks,12±1 Weeks
DLTs related to hUC-MSC-sEV include adverse events of grade 3 or higher (including significant clinical laboratory findings) that are possibly, likely, or definitely related to the study drug, accompanied by clinical symptoms and requiring medical treatment within 14 days of administration. Adverse events are graded according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).
次要结局
- Incidence of severe adverse events(4±1 Weeks, 8±1 Weeks,12±1 Weeks)
- American Spinal Injury Association(ASIA) Score(4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months)
- Klekamp and Sammi syringomyelia scale(4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months)
- Time to event (death, tracheostomy, and permanent assisted mechanical ventilation)(up to 12 months)
- modified Japanese Orthopaedic Association Scores (mJOA)(4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months)
- xuanwu syringomyelia scale(4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months)
- improvement or resolution of the syrinx(4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months)