Clinical trial NCT03003364: Intrathecal Administration of Expanded Wharton's Jelly Mesenchymal Stem Cells in Chronic Traumatic Spinal Cord Injury
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injury, Chronic
Lead sponsor: Banc de Sang i Teixits
Sponsor class: OTHER
Collaborators: name: Hospital de Neurorehabilitació Institut Guttmann
name: Recerca Clínica S.L.
name: Syntax for Science, S.L
First posted: 2016-12-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: 12 months
Secondary outcomes:
measure: Extent and severity of a patient's spinal cord injury
timeFrame: 6 months
measure: Motor electrophysiology assessment
timeFrame: 6 month
measure: Somatosensory electrophysiology assessment
timeFrame: 6 month
measure: Electrical nerve stimulation on pain perception
timeFrame: 6 month
measure: Mictional dysfunction
timeFrame: 6 month
measure: Anal sphincter integrity
timeFrame: 6 month
measure: Neuropathic pain
timeFrame: 6 months
measure: Spasticity
timeFrame: 6 months
measure: Functionality
timeFrame: 6 months
measure: Quality of life (individual overall perception of quality of life, individual overall perception of their health, Physical health, Psychological, Social relationships, Environment)
timeFrame: 6 months
measure: Urinary disorder
timeFrame: 6 months
measure: Size injury
timeFrame: 12 months
measure: Presence of allogeneic cells
timeFrame: 1 month
measure: Immunology
timeFrame: 1 months
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital de Neurorehabilitació Institut Guttmann
state: Barcelona
Study officials:
affiliation: Hospital de Neurorehabilitació Institut Guttmann
name: Joan Vidal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.