Intrathecal Administration of Expanded Wharton's Jelly Mesenchymal Stem Cells in Chronic Traumatic Spinal Cord Injury

Study Overview
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Brief Summary
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This is a phase I/IIa, randomized, double-blind, two-arms, two-dose administration, placebo controlled, two-way crossover clinical trial in which 10 patients from 18 to 65 years of age affected with chronic traumatic spinal cord will enter the study with the objective to assess the safety and to obtain efficacy data in intrathecal administration of expanded Wharton's jelly mesenchymal stem cells.

Detailed Description
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This is a phase I/IIa, randomized, double-blind, two-arms, two-dose administration, placebo controlled, clinical trial in which 10 patients from 18 to 65 years of age affected with chronic traumatic spinal cord will enter the study with the objective to assess the safety and to obtain efficacy data in intrathecal administration (L3 level) of expanded Wharton's jelly mesenchymal stem cells. Following the administration patients will remain for 24 h at the hospital and thereafter will be discharged. For the first period, the follow-up is planned at day 7 and at 1, 3 and 6 months. At month 6, the patients will be treated in a crossover way (second period) and will follow the same schedule for the follow-up. First clinical trial evaluation will be performed at 12 month follow-up. From 12 to 18 month after the first infusion, patients will be randomized again to active treatment or placebo (double-blind) in order to assess the safety and efficacy of a second dose at 12 month follow-up. Thereafter, patients will be followed up at 24 and 36 months as part of a long-term follow-up.

Official Title
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A Phase I/IIa, Randomized, Double-blind, Single-dose, Placebo Controlled, Two-way Crossover Clinical Trial to Assess the Safety and to Obtain Efficacy Data in Intrathecal Administration of Expanded Wharton's Jelly Mesenchymal Stem Cells in Chronic Traumatic Spinal Cord Injury

Conditions
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Spinal Cord Injury, Chronic

Intervention / Treatment
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* Drug: XCEL-UMC-BETA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single spinal cord injury lesion caused by trauma Affected cord segments between T2 and T11, confirmed by magnetic resonance Complete paraplegia (ASIA A) Chronic disease state (between 12 months and 5 years after the injury) Patients from 18 to 65 years of age, both sexes Life expectancy > 2 years Confidence that the patient will attend the follow-up visits. Given informed consent in writing Patient is able to understand the study and its procedures Exclusion Criteria: Mechanic ventilation Lesion affecting multiple levels Lesion length superior to 3 spinal cord segments, assessed by magnetic resonance Penetrating trauma affecting the spinal cord Positive serology to HIV, HBV, HCV and or syphilis Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding Use of metal implants that complicates the MRI interpretation Planned spinal surgery within subsequent 24 month after entering the trial Intrathecal medication or immunosuppressive drugs the previous 60 days. Neurodegenerative diseases Significant abnormal laboratory tests that contraindicates patient's participation in the study. Neoplasia within the previous 5 years, or without complete remission Patient with difficulty for communicating Participation in another clinical trial or treated with an investigational medicinal product the previous 60 days Contraindication for lumbar punction Other pathologic conditions or circumstances that could complicate the participation of the patient in the study according to medical criteria The patient does not accept to be followed-up for a period that could exceed the clinical trial length

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: XCEL-UMC-BETA/placebo<br>Ex vivo cultured human mesenchymal stem cells from Wharton jelly, in a blinded syringe (initial treatment) / Placebo (month 6) | Drug: XCEL-UMC-BETA<br>* Intrathecal allogeneic cell therapy in a blinded syringe<br>* Other names: Expanded MSC from Wharton Jelly;Drug: Placebo<br>* Placebo in a blinded syringe<br>|
| Placebo Comparator: Placebo/XCEL-UMC-BETA<br>Placebo in a blinded syringe (initial treatment) / XCEL-UMC-BETA (month 6) | Drug: XCEL-UMC-BETA<br>* Intrathecal allogeneic cell therapy in a blinded syringe<br>* Other names: Expanded MSC from Wharton Jelly;Drug: Placebo<br>* Placebo in a blinded syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Adverse events | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent and severity of a patient's spinal cord injury | ASIA Impairment Scale | 6 months | 
| Motor electrophysiology assessment | Evoked potentials | 6 month | 
| Somatosensory electrophysiology assessment | Evoked potentials | 6 month | 
| Electrical nerve stimulation on pain perception | Pain threshold perception | 6 month | 
| Mictional dysfunction | Urodynamic testing | 6 month | 
| Anal sphincter integrity | Anorectal manometry test | 6 month | 
| Neuropathic pain | Numerical scale (0 to 10) | 6 months | 
| Spasticity | Modified Ashworth scale | 6 months | 
| Functionality | SCIM III scale | 6 months | 
| Quality of life (individual overall perception of quality of life, individual overall perception of their health, Physical health, Psychological, Social relationships, Environment) | WHOQOL BREF questionnaire | 6 months | 
| Urinary disorder | Qualiveen questionnaire | 6 months | 
| Size injury | Magnetic Resonance Imaging | 12 months | 
| Presence of allogeneic cells | Chimerism in cerebrospinal fluid | 1 month | 
| Immunology | Antibodies anti-HLA in peripherical blood and in cerebrospinal fluid | 1 months |