The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial
Authors: Zarrabi Morteza , Akbari Masood Ghahvechi , Amanat Man , Majmaa Anahita , Moaiedi Ali Reza , Montazerlotfelahi Hadi , Nouri Masoumeh , Hamidieh Amir Ali , Badv Reza Shervin , Karimi Hossein , Rabbani Ali , Mohebbi Ali , Rahimi-Dehgolan Shahram , Rahimi Rosa , Dehghan Ensieh , Vosough Massoud , Abroun Saeed , Shamsabadi Farhad Mahvelati , Tavasoli Ali Reza , Alizadeh Houman , Pak Neda , Zamani Gholam Reza , Mohammadi Mahmoud , Javadzadeh Mohsen , Ghofrani Mohammad , Hassanpour Seyed Hossein , Heidari Morteza , Taghdiri Mohammad Mehdi , Mohseni Mohamad Javad , Noparast Zahra , Masoomi Safdar , Goudarzi Mehrdad , Mohamadpour Masood , Shodjaee Razieh , Samimi Solaleh , Mohammad Monireh , Gholami Mona , Vafaei Nahid , Koochakzadeh Leyli , Valizadeh Amir , Malamiri Reza Azizi , Ashrafi Mahmoud Reza 
Published: March 2022

Abstract
Introduction
The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure.

Methods
Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint.

Results
There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (β: 7.10; 95%CI: 2.08, 12.76; Cohen’s d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (β: -0.58; 95%CI: -1.18, -0.11; Cohen’s d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up.

Conclusions
This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP.

Trial Registration
The study was registered with ClinicalTrials.gov (NCT03795974).