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

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

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury, Chronic
• Intervention / Treatment: Drug: XCEL-UMC-BETA; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital de Neurorehabilitació Institut Guttmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Single spinal cord injury lesion caused by trauma
2. Affected cord segments between T2 and T11, confirmed by magnetic resonance
3. Complete paraplegia (ASIA A)
4. Chronic disease state (between 12 months and 5 years after the injury)
5. Patients from 18 to 65 years of age, both sexes
6. Life expectancy > 2 years
7. Confidence that the patient will attend the follow-up visits.
8. Given informed consent in writing
9. Patient is able to understand the study and its procedures

Exclusion Criteria:

1. Mechanic ventilation
2. Lesion affecting multiple levels
3. Lesion length superior to 3 spinal cord segments, assessed by magnetic resonance
4. Penetrating trauma affecting the spinal cord
5. Positive serology to HIV, HBV, HCV and or syphilis
6. Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding
7. Use of metal implants that complicates the MRI interpretation
8. Planned spinal surgery within subsequent 24 month after entering the trial
9. Intrathecal medication or immunosuppressive drugs the previous 60 days.
10. Neurodegenerative diseases
11. Significant abnormal laboratory tests that contraindicates patient's participation in the study.
12. Neoplasia within the previous 5 years, or without complete remission
13. Patient with difficulty for communicating
14. Participation in another clinical trial or treated with an investigational medicinal product the previous 60 days
15. Contraindication for lumbar punction
16. Other pathologic conditions or circumstances that could complicate the participation of the patient in the study according to medical criteria
17. The patient does not accept to be followed-up for a period that could exceed the clinical trial length

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Banc de Sang i Teixits
• Collaborators: Syntax for Science, S.L; Hospital de Neurorehabilitació Institut Guttmann; Recerca Clínica S.L.
• Investigators: Principal Investigator: Joan Vidal, MD, PhD, Hospital de Neurorehabilitació Institut Guttmann

Publications and helpful links

General Publications

• Albu S, Kumru H, Coll R, Vives J, Valles M, Benito-Penalva J, Rodriguez L, Codinach M, Hernandez J, Navarro X, Vidal J. Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study. Cytotherapy. 2021 Feb;23(2):146-156. doi: 10.1016/j.jcyt.2020.08.008. Epub 2020 Sep 25.

Helpful Links

• Blood and Tissue Bank of Catalonia
• Hospital de Neurorehabilitació Institut Guttmann
• Marató TV3

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2016
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): February 11, 2020

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimate): December 28, 2016

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: XCEL-SCI-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No