Repeated Subarachnoid Administrations of hUC-MSCs in Treating SCI

• ClinicalTrials.gov Identifier: NCT02481440
• Recruitment Status: Completed
• First Posted: June 25, 2015
• Results First Posted: June 30, 2020
• Last Update Posted: June 30, 2020
• Sponsor: Limin Rong
• Information provided by (Responsible Party): Limin Rong, Third Affiliated Hospital, Sun Yat-Sen University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injuries	Biological: human umbilical cord mesenchymal stem cells (hUC-MSCs)	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Repeated Subarachnoid Administrations of Human Umbilical Cord Mesenchymal Stem Cells in Treating Spinal Cord Injury
• Actual Study Start Date: March 30, 2018
• Actual Primary Completion Date: March 31, 2020
• Actual Study Completion Date: March 31, 2020

Arms and Interventions

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 Name: umbilical cord mesenchymal stem cells

Outcome Measures

Primary Outcome Measures :

1. American Spinal Injury Association (ASIA) Total Score at the Fourth Follow-up [ Time Frame: 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.
2. SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score at the Fourth Follow-up [ Time Frame: 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 Outcome Measures :

1. American Spinal Injury Association (ASIA) Total Score [ Time Frame: 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.
2. SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score [ Time Frame: 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.
3. International Standards to Document Remaining Autonomic Function After Spinal Cord Injury (ISAFSCI) Score [ Time Frame: 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.
4. Penn Scale [ Time Frame: 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.
5. Modified Ashworth Scale [ Time Frame: 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.
6. Geffner Scale [ Time Frame: 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.
7. Neurogenic Bowel Dysfunction (NBD) Scale [ Time Frame: 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.
8. Residual Urine Volume [ Time Frame: at first transplantation and 12 months following the final administration of hUC-MSCs ]
   Ultrasonic examination is used to assess residual urine volume

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

China, Guangdong

The Third Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, China, 510630

Sponsors and Collaborators

Limin Rong

Investigators

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

  Study Documents (Full-Text)

Documents provided by Limin Rong, Third Affiliated Hospital, Sun Yat-Sen University:

Study Protocol and Statistical Analysis Plan  [PDF] May 1, 2020

More Information

• Responsible Party: Limin Rong, Director of Spine Surgery Department, Third Affiliated Hospital, Sun Yat-Sen University
• ClinicalTrials.gov Identifier: NCT02481440
• Other Study ID Numbers: hUC-MSC-SCI
• First Posted: June 25, 2015
• Results First Posted: June 30, 2020
• Last Update Posted: June 30, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Limin Rong, Third Affiliated Hospital, Sun Yat-Sen University:

human umbilical cord mesenchymal stem cells; spinal cord injury

Additional relevant MeSH terms:

Spinal Cord Injuries; Wounds and Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System