Syringomyelia
Conditions
Keywords
syringomyelia, spinal cord injury, mesenchymal stromal cell, extracellular vesicle
Brief summary
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.
Detailed description
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.
Interventions
DRUGExosomes group
Exosomes derived from human umbilical cord blood mesenchymal stem cells for Intrathecal injection (administered once a month, for a total of three months, based on the recommended dose during the dose-escalation phase).
Sponsors
Xuanwu Hospital, Beijing
Yisaier Medical Technology (shan xi) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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;
Exclusion criteria
* 1\. Those with diabetes, heart disease, or impaired liver or kidney function; 2. Those with other diseases such as brainstem tumors and spinal cord tumors; 3. Infected individuals with lumbar puncture sites; 4. Those with previous or detected abnormalities in the heart; 5. Those who have autoimmune diseases and need to be treated with immunosuppressants; 6. Those who are allergic to the research drugs; 7. Have participated in other interventional clinical studies or received other cell therapies (excluding blood transfusion) within the past three months; 8. 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; 9. Pregnant women, women who are breastfeeding and those planning to become pregnant; 10. Serological tests (HBsAg, anti-HCV, anti-HIV, TP-Ab) are positive; 11. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who experienced dose-limiting Toxicities (DLTs) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| American Spinal Injury Association(ASIA) Score | 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months | American Spinal Injury Association(ASIA) Score for evaluating the spinal cord function， degree of the spinal cord function, motor1-100, sensory 1-224, higher scores mean a better outcome |
| Klekamp and Sammi syringomyelia scale | 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months | for evaluating the spinal cord function, each score 1-5, higher scores mean a better outcome |
| Incidence of severe adverse events | 4±1 Weeks, 8±1 Weeks,12±1 Weeks | The proportion of patients who experienced severe adverse events. |
| Time to event (death, tracheostomy, and permanent assisted mechanical ventilation) | up to 12 months | The number of time-to-event outcomes. |
| modified Japanese Orthopaedic Association Scores (mJOA) | 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months | Motor function， sensory， bladder function；for evaluating the spinal cord function；0-17， higher scores mean a better outcome |
| xuanwu syringomyelia scale | 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months | for evaluating the spinal cord function, for evaluating the spinal cord function；0-18， higher scores mean a worse outcome |
| improvement or resolution of the syrinx | 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months | improvement in size. |
Countries
China
Outcome results
None listed