Repeated Subarachnoid Administrations of hUC-MSCs in Treating SCI

Repeated Subarachnoid Administrations of Human Umbilical Cord Mesenchymal Stem Cells in Treating Spinal Cord Injury

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Biological: human umbilical cord mesenchymal stem cells (hUC-MSCs)

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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hUC-MSC Transplantation; Repeated 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	Biological: human umbilical cord mesenchymal stem cells (hUC-MSCs); Four times of intrathecal administrations of hUC-MSCs; Other Names: umbilical cord mesenchymal stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	at 12 months following the final administration of hUC-MSCs
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.	at 12 months following the final administration of hUC-MSCs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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) 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.	at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs
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.	at first transplantation and 12 months following the final administration of hUC-MSCs
Penn Scale	Penn scale form is used to assess muscle spasm (Range: 0-4 scores). The higher scores mean a worse outcome.	at first transplantation and 12 months following the final administration of hUC-MSCs
Modified Ashworth Scale	Modified Ashworth scale form is used to assess muscle spasticity (Range: 0-16 scores). The higher scores mean a worse outcome.	at first transplantation and 1, 3, 12 months following the final administration of hUC-MSCs
Geffner Scale	Geffner scale form is used to assess bladder function (Range: 0-7 scores). The higher scores mean a better outcome.	at first transplantation and 12 months following the final administration of hUC-MSCs
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.	at first transplantation and 12 months following the final administration of hUC-MSCs
Residual Urine Volume	Ultrasonic examination is used to assess residual urine volume	at first transplantation and 12 months following the final administration of hUC-MSCs

Collaborators and Investigators

• Sponsor: Limin Rong
• Investigators: Principal Investigator: Min Li Rong, M.D., Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2018
• Primary Completion (Actual): March 31, 2020
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): June 30, 2020
• Last Update Submitted That Met QC Criteria: June 13, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: spinal cord injury; human umbilical cord mesenchymal stem cells
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: hUC-MSC-SCI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No