Repeated Subarachnoid Administrations of Human Umbilical Cord Mesenchymal Stem Cells in Treating Spinal Cord Injury
Phase: PHASE1
Conditions: Spinal Cord Injuries
Sponsor: Limin Rong

ClinicalTrials.gov: NCT02481440
Unique Protocol ID: hUC-MSC-SCI
Official Title: Repeated
Subarachnoid
Administrations
of
Human
Umbilical Cord Mesenchymal Stem Cells in Treating Spinal Cord Injury
Document Date: May 1st, 2020

Study protocol
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 1×106 cells/kg. For the first administration of stem
cells, maximum lumbar flexion of subject was maintained, and cerebrospinal fluid
(CSF) release with a volume of approximately 10 ml was performed. hUC-MSCs
suspension was administered manually at L4/5 level as slowly as possible. This was
followed by a two-minute delay before the injection needle was withdrawn. One
month later, subject underwent a second subarachnoid engraftment of hUC-MSCs.
Following this pattern, subject received the third and fourth stem cell transplantation.
During the intervention period of four months, all subjects received the standardized
care. 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. 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 AE
with hUC-MSCs administration were identified. Efficacy indicators included ASIA
score and the SCI Functional Rating Scale of the International Association of
Neurorestoratology (IANR-SCIFRS) for the recovery of spinal cord function; the

International Standards to document remaining Autonomic Function after Spinal Cord
Injury (ISAFSCI); Penn and modified Ashworth scales for the evaluation of spasms
and spasticity of affected muscles; Geffner scale for the study of bladder function and
Neurogenic Bowel Dysfunction (NBD) scale; residual urine volume (RUV). In this
trial, ASIA and IANR-SCIFRS total scores at the fourth follow-up were determined as
primary outcomes, while these two indicators at the remaining time points and the
other efficacy indicators were secondary outcomes.

Statistical analysis
Continuous variables were expressed as means ± standard deviations or median
with interquartile range according to their normality, while categorical data were
given as frequencies. In terms of efficacy indicators collected at multiple (≥3) time
points, analysis of variance (ANOVA) for repeated measurement or Friedman test was
used to detect overall statistical significance of normal or non-normal continuous data.
Following the Bonferroni correction, the paired samples t-test and Wilcoxon signed
ranks test were applied to analyze normal and non-normal continuous variables,
respectively. Subgroup analysis of two primary efficacy indicators (ASIA and
IANR-SCIFRS total scores at the fourth follow-up) were performed. Statistical
Product and Service Solutions (SPSS v. 22.0) was used to perform all statistical
analyses, and P<0.05 was considered statistically significant.