Spinal Cord Injuries
Conditions
Keywords
human umbilical cord mesenchymal stem cells, spinal cord injury
Brief summary
The purpose of this study is to evaluate the safety and efficacy of repeated intrathecal administrations of allogeneic human umbilical cord mesenchymal stem cells for the treatment of spinal cord injury.
Detailed description
Spinal cord injury (SCI) is a devastating disease and often leads to lifelong disability, muscle spasm, sensory deficits, autonomic disturbances, as well as bowel and bladder incontinence, all of which can cause tremendous troubles to patients but are lack of any effective treatment up to now. SCI is not only a severe healthy problem but also a great social burden. To the best of our knowledge, cell therapy seems to be a promising alternative for the treatment of SCI due to numerous advantages. However, cytotherapy is still in its infancy since there are many disparities and uncertainties regarding subject selection, cellular type, transplantation timing, administration dose and deliver route in clinical trial protocols. Hence, a standardized well-designed clinical study is urgently required for the safe and effective treatment of SCI. In this study, complete or incomplete cervical, thoracic, and thoracolumbar SCI subjects were recruited to join in a prospective, single-center, single-arm clinical trial. Intervention is four times of subarachnoid administration of allogeneic hUC-MSCs. During the intervention and follow-up periods of this trial, any adverse event was identified rapidly and managed properly. The maximum intensity and relationship of any adverse event with hUC-MSCs administration were identified.The primary efficacy indicator is American spinal injury association (ASIA) total score at the fourth follow-up and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total score at the fourth follow-up. Secondary efficacy indicators are these two indicators at the remaining time points, scores of pin prick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume. Subgroup analysis of primary efficacy indicators was also performed. In this trial, informed consent forms that had the approval of the institutional review board were obtained from all participants before recruitment. In this clinical study, subarachnoid transplantation of hUC-MSCs was performed a total of four times per subject with the delivery dose of 1×10E6 cells/kg. After the completion of cytotherapy, subject was regularly followed up in the hospital at four time points, determined at 1, 3, 6, and 12 months following the final administration of hUC-MSCs. At each time point of administration (the first, second, third, and fourth transplantation) and follow-up (the first, second, third, and fourth follow-up), safety and efficacy indicators were collected accordingly by two independent assessors.
Interventions
BIOLOGICALhuman umbilical cord mesenchymal stem cells (hUC-MSCs)
Four times of intrathecal administrations of hUC-MSCs
Sponsors
Limin Rong
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. complete or incomplete trauma-induced SCI \[American Spinal Injury Association (ASIA) Impairment Scale classification: A-D\] that happened at least two months before recruitment; 2. aged between 18 and 65 years; 3. agreed to participate in this study voluntarily and be regularly followed up for 12 months after the completion of hUC-MSCs administration
Exclusion criteria
1. ankylosing spondylitis, myelitis, or vascular abnormalities within the spinal cord parenchyma; 2. severe comorbidities, including but not limited to craniocerebral injury, cutaneous back infection, psychiatric disease, or cancer; 3. pregnancy or lactation (for females); 4. predicted lifespan of less than 12 months following the end of hUC-MSCs transplantation; 5. participation in any other stem cell-related clinical trials that might affect accurate neurological evaluations in the present trial; 6. any medical condition that, in the opinion of investigators, may pose a safety risk to any subject in this study, confound safety or efficacy assessments, or interfere with study participation Rejection Criteria: 1. misdiagnosis; 2. use of any medication that may significantly impact the assessment accuracy of stem cell engraftment; 3. absence of any evaluation outcome at any time point during the follow-up period Cessation Criteria: 1. individual wishes of the subjects; 2. occurrence of any stem cell-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; 3. detection of any major mistake in the present protocol during the implementation of this clinical trial; 4. the national administration agency requires the clinical trial to be halted
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| American Spinal Injury Association (ASIA) Total Score at the Fourth Follow-up | at 12 months following the final administration of hUC-MSCs | American Spinal Injury Association (ASIA) form is used to assess ASIA total score (Range: 0-324 scores). The higher scores mean a better outcome. |
| SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score at the Fourth Follow-up | at 12 months following the final administration of hUC-MSCs | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) form is used to assess IANR-SCIFRS total score (Range: 0-51 scores). The higher scores mean a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| International Standards to Document Remaining Autonomic Function After Spinal Cord Injury (ISAFSCI) Score | at first transplantation and 12 months following the final administration of hUC-MSCs | International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) form is used to assess ISAFSCI score (autonomic nervous function) (Range: 5-32 scores). The higher scores mean a better outcome. |
| Penn Scale | at first transplantation and 12 months following the final administration of hUC-MSCs | Penn scale form is used to assess muscle spasm (Range: 0-4 scores). The higher scores mean a worse outcome. |
| Modified Ashworth Scale | at first transplantation and 1, 3, 12 months following the final administration of hUC-MSCs | Modified Ashworth scale form is used to assess muscle spasticity (Range: 0-16 scores). The higher scores mean a worse outcome. |
| American Spinal Injury Association (ASIA) Total Score | at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs | American Spinal Injury Association (ASIA) form is used to assess ASIA total score (Range: 0-324 scores). The higher scores mean a better outcome. |
| Neurogenic Bowel Dysfunction (NBD) Scale | at first transplantation and 12 months following the final administration of hUC-MSCs | Neurogenic Bowel Dysfunction (NBD) scale form is used to assess bowel function (Range: 0-47 scores). The higher scores mean a worse outcome. |
| Residual Urine Volume | at first transplantation and 12 months following the final administration of hUC-MSCs | Ultrasonic examination is used to assess residual urine volume |
| Geffner Scale | at first transplantation and 12 months following the final administration of hUC-MSCs | Geffner scale form is used to assess bladder function (Range: 0-7 scores). The higher scores mean a better outcome. |
| SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) form is used to assess IANR-SCIFRS total score (Range: 0-51 scores). The higher scores mean a better outcome. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| hUC-MSC Transplantation Four times of intrathecal administrations of 1x10E6 human umbilical cord mesenchymal stem cells per kg in subjects with spinal cord injury with an interval of one month between each administration | 41 |
| Total | 41 |
Baseline characteristics
| Characteristic | hUC-MSC Transplantation | — |
|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 11 | — |
| Chronicity of SCI | 45.15 months STANDARD_DEVIATION 59.78 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment China | 41 participants | — |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 33 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 102 |
| other Total, other adverse events | 44 / 102 |
| serious Total, serious adverse events | 0 / 102 |
Outcome results
Primary
American Spinal Injury Association (ASIA) Total Score at the Fourth Follow-up
American Spinal Injury Association (ASIA) form is used to assess ASIA total score (Range: 0-324 scores). The higher scores mean a better outcome.
Time frame: at 12 months following the final administration of hUC-MSCs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score at the Fourth Follow-up | 183.88 score | Standard Deviation 69.76 |
Primary
SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score at the Fourth Follow-up
SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) form is used to assess IANR-SCIFRS total score (Range: 0-51 scores). The higher scores mean a better outcome.
Time frame: at 12 months following the final administration of hUC-MSCs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score at the Fourth Follow-up | 29.49 score | Standard Deviation 10.47 |
Secondary
American Spinal Injury Association (ASIA) Total Score
American Spinal Injury Association (ASIA) form is used to assess ASIA total score (Range: 0-324 scores). The higher scores mean a better outcome.
Time frame: at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 1st transplantation | 158.15 score | Standard Deviation 70.93 |
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 3rd follow-up | 182.44 score | Standard Deviation 71 |
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 2nd follow-up | 178.39 score | Standard Deviation 71.51 |
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 1st follow-up | 176.05 score | Standard Deviation 71.88 |
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 4th transplantation | 172.00 score | Standard Deviation 73.51 |
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 3rd transplantation | 168.41 score | Standard Deviation 74.16 |
| hUC-MSC Transplantation | American Spinal Injury Association (ASIA) Total Score | 2nd transplantation | 163.80 score | Standard Deviation 72.53 |
Secondary
Geffner Scale
Geffner scale form is used to assess bladder function (Range: 0-7 scores). The higher scores mean a better outcome.
Time frame: at first transplantation and 12 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| hUC-MSC Transplantation | Geffner Scale | 4th follow-up | 3 score |
| hUC-MSC Transplantation | Geffner Scale | 1st transplantation | 2 score |
Secondary
International Standards to Document Remaining Autonomic Function After Spinal Cord Injury (ISAFSCI) Score
International Standards to document remaining Autonomic Function after Spinal Cord Injury (ISAFSCI) form is used to assess ISAFSCI score (autonomic nervous function) (Range: 5-32 scores). The higher scores mean a better outcome.
Time frame: at first transplantation and 12 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| hUC-MSC Transplantation | International Standards to Document Remaining Autonomic Function After Spinal Cord Injury (ISAFSCI) Score | 4th follow-up | 12 score |
| hUC-MSC Transplantation | International Standards to Document Remaining Autonomic Function After Spinal Cord Injury (ISAFSCI) Score | 1st transplantation | 11 score |
Secondary
Modified Ashworth Scale
Modified Ashworth scale form is used to assess muscle spasticity (Range: 0-16 scores). The higher scores mean a worse outcome.
Time frame: at first transplantation and 1, 3, 12 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| hUC-MSC Transplantation | Modified Ashworth Scale | 4th follow-up | 2 score |
| hUC-MSC Transplantation | Modified Ashworth Scale | 2nd follow-up | 2 score |
| hUC-MSC Transplantation | Modified Ashworth Scale | 1st follow-up | 2.5 score |
| hUC-MSC Transplantation | Modified Ashworth Scale | 1st transplantation | 3 score |
Secondary
Neurogenic Bowel Dysfunction (NBD) Scale
Neurogenic Bowel Dysfunction (NBD) scale form is used to assess bowel function (Range: 0-47 scores). The higher scores mean a worse outcome.
Time frame: at first transplantation and 12 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| hUC-MSC Transplantation | Neurogenic Bowel Dysfunction (NBD) Scale | 4th follow-up | 3 score |
| hUC-MSC Transplantation | Neurogenic Bowel Dysfunction (NBD) Scale | 1st transplantation | 6 score |
Secondary
Penn Scale
Penn scale form is used to assess muscle spasm (Range: 0-4 scores). The higher scores mean a worse outcome.
Time frame: at first transplantation and 12 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| hUC-MSC Transplantation | Penn Scale | 4th follow-up | 1 score |
| hUC-MSC Transplantation | Penn Scale | 1st transplantation | 1 score |
Secondary
Residual Urine Volume
Ultrasonic examination is used to assess residual urine volume
Time frame: at first transplantation and 12 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| hUC-MSC Transplantation | Residual Urine Volume | 4th follow-up | 27.90 ml |
| hUC-MSC Transplantation | Residual Urine Volume | 1st transplantation | 67.65 ml |
Secondary
SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score
SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) form is used to assess IANR-SCIFRS total score (Range: 0-51 scores). The higher scores mean a better outcome.
Time frame: at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 3rd follow-up | 28.93 score | Standard Deviation 10.26 |
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 2nd follow-up | 28.44 score | Standard Deviation 10.28 |
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 1st follow-up | 27.56 score | Standard Deviation 10.03 |
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 4th transplantation | 26.85 score | Standard Deviation 10.36 |
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 2nd transplantation | 25.71 score | Standard Deviation 10.32 |
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 1st transplantation | 24.54 score | Standard Deviation 9.82 |
| hUC-MSC Transplantation | SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score | 3rd transplantation | 26.05 score | Standard Deviation 10.15 |