Clinical trial NCT02481440: Repeated Subarachnoid Administrations of hUC-MSCs in Treating SCI
Official title: Repeated Subarachnoid Administrations of Human Umbilical Cord Mesenchymal Stem Cells in Treating Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injuries
Keywords: human umbilical cord mesenchymal stem cells
spinal cord injury
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2015-06-25
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: American Spinal Injury Association (ASIA) Total Score at the Fourth Follow-up
timeFrame: at 12 months following the final administration of hUC-MSCs
measure: SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score at the Fourth Follow-up
timeFrame: at 12 months following the final administration of hUC-MSCs
Secondary outcomes:
measure: American Spinal Injury Association (ASIA) Total Score
timeFrame: at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs
measure: SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) Total Score
timeFrame: at first, second, third, and fourth transplantation and 1, 3, 6 months following the final administration of hUC-MSCs
measure: International Standards to Document Remaining Autonomic Function After Spinal Cord Injury (ISAFSCI) Score
timeFrame: at first transplantation and 12 months following the final administration of hUC-MSCs
measure: Penn Scale
timeFrame: at first transplantation and 12 months following the final administration of hUC-MSCs
measure: Modified Ashworth Scale
timeFrame: at first transplantation and 1, 3, 12 months following the final administration of hUC-MSCs
measure: Geffner Scale
timeFrame: at first transplantation and 12 months following the final administration of hUC-MSCs
measure: Neurogenic Bowel Dysfunction (NBD) Scale
timeFrame: at first transplantation and 12 months following the final administration of hUC-MSCs
measure: Residual Urine Volume
timeFrame: at first transplantation and 12 months following the final administration of hUC-MSCs
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Third Affiliated Hospital, Sun Yat-Sen University
name: Min Li Rong, M.D.
role: PRINCIPAL_INVESTIGATOR
References: