Cell Therapy for Chronic Traumatic Cervical Incomplete Spinal Cord Injury

Phase 1

Completed

• Conditions: Spinal Cord Injury Cervical
• Interventions: Drug: Placebo; Drug: WJ-MSC (XCEL-UMC-BETA)

• Registration Number: NCT05054803
• Lead Sponsor: Banc de Sang i Teixits

Brief Summary

This is a double-blind, randomized, placebo-controlled, multicenter clinical trial in which 18 patients affected with chronic traumatic incomplete cervical spinal cord injury will be randomized to either the active treatment (2 doses of intrathecal WJ-MSC 3 months apart) or to placebo (2 intrathecal infusions, 3 months apart). Thereafter, patients will be followed-up for 12 months for safety and efficacy assessment.

Detailed Description

Double-blind, randomized, placebo-controlled, multicenter clinical trial that will include 18 patients affected with chronic traumatic incomplete cervical spinal cord injury who will be randomized 1:1, stratified by center, to one of the 2 treatment arms of the study: WJ-MSC / WJ-MSC (at a dose of 1E6 ± 30% live cells / Kg of weight) or Placebo / placebo. Medication will be administered intrathecally at day 1 and at 3 months. The main objective of the trial is to assess safety at a 12-month follow-up. Secondary objectives include the evaluation of efficacy through clinical response, electrophysiological changes, questionnaires of functionality and quality of life, as well as the presence of anti-HLA antibodies and donor cellularity in the cerebrospinal fluid.

Study Timeline

• Study First Submitted: 2021-09-14
• Study First Submitted QC: 2021-09-14
• Study First Posted: 2021-09-23
• Study Start: 2021-10-13
• Status Verified: 2024-01
• Primary Completion: 2024-01-20
• Study Completion: 2024-01-20
• Last Update Submitted: 2024-01-23
• Last Update Posted: 2024-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Single spinal cord injury lesion caused by trauma
2. Affected cord segments between C1 and T1, confirmed by magnetic resonance
3. Incomplete lesion (ASIA B, C or D)
4. Chronic disease state (between 1 and 5 years after the injury)
5. Patients from 18 to 70 years of age, both sexes
6. Life expectancy > 2 years
7. Residence near the center during study participation and 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. Penetrating trauma affecting the spinal cord
3. Pregnant woman or without proper anticonceptive measures according to the investigator, or breath feeding
4. Planned spinal surgery within subsequent 12 month after entering the trial
5. Neurodegenerative diseases
6. Significant abnormal laboratory tests that contraindicates patient's participation in the study
7. Neoplasia within the previous 5 years, or without complete remission
8. Patient with communication difficulties
9. Simultaneous participation in another clinical trial or treated with an investigational medicinal product the previous 30 days, that could interfere in the results of the study
10. Previous treatment with and advanced Therapy Medicinal Product (cell therapy)
11. Contraindication for lumbar punction
12. Contraindication or inability to follow a rehabilitation program
13. Other pathologic conditions or circumstances that difficult participation in the study according to medical criteria
14. The patient does not accept to be followed-up for a period that could exceed the clinical trial length

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Pre-filled syringe with 4 ± 1 mL containing a balanced saline solution supplemented with human albumin
WJ-MSC (XCEL-UMC-BETA)	WJ-MSC (XCEL-UMC-BETA)	Pre-filled syringe with 4 ± 1 mL containing WJ-MSC in a balanced saline solution supplemented with human albumin.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events	At 12 month follow-up	Adverse events

Secondary Outcome Measures

Name	Time	Method
Modified Ashworth scale for spasticity	At 6 and 12 month follow-up	Changes in the modified Ashworth scale score with respect to baseline value. It is a 5 point numerical scale that graded spasticity from 0 to 4, with 0 being no resistance and 4 being a limb rigid in flexion or extension, and includes a 1+ value.
Electrical pain threshold perception	At 6 and 12 month follow-up	Changes in electrical pain threshold perception score with respect to baseline. Lower scores mean a better outcome
Walking index for spinal cord injury (WISCI II)	At 6 and 12 month follow-up	Changes in the walk test WISCIII score with respect to baseline value. The score ranges from 0 (most severe impairment) to 20 (least severe impairment)
Motor evoked potentials	At 6 and 12 month follow-up	Changes in motor evoked potentials score with respect to baseline value. Higher scores mean a better outcome
Handgrip Strength	At 6 and 12 month follow-up	Will be assessed using a dynamometer. Changes in the score with respect to baseline values. Higher scores mean a better outcome
Numerical scale for neuropathic pain assessment	At 6 and 12 month follow-up	Changes in the numerical scale for neuropathic pain score with respect to baseline value. Score ranges from 0 (no pain) to 10 (unbearable pain)
American Spinal Injury Association (ASIA) impairment scale	At 1, 3, 4, 6 and 12 month follow-up	Changes in ASIA score with respect to baseline value as detailed at https://asia-spinalinjury.org/international-standards-neurological-classification-sci-isncsci-worksheet/
Somatosensory evoked potentials	At 6 and 12 month follow-up	Changes in somatosensory evoked potentials score with respect to baseline value. Higher scores mean a better outcome
Psychological general well-being index (PGWBI)	At 12 month follow-up	Changes in the PGWBI score with respect to baseline value. Score ranges from 0 to 132, with higher scores meaning a better outcome.
Hospital Anxiety and Depression Scale (HADS)	At 12 month follow-up	Changes in the HADS score with respect to baseline value. This is a 14-item self-administered questionnaire containing 2 subscales (one for anxiety and one for depression), with a score range of each subscale from 0-21. Higher score indicates higher anxiety and depression.
Community Integration Questionaire (CIQ-IG)	At 12 month follow-up	Changes in the CIQ-IG score with respect to baseline value. Score ranges from 0 to 25, with higher scores meaning a better outcome.
Spinal Cord Independence Measure III (SCIM III)	At 6 and 12 month follow-up	Changes in the SCIM III scale score with respect to baseline value. Score ranges from 0 to 20 with higher scores meaning better outcome.
World Health Organization Quality of life questionnaire (WHOQOL-BREF)	At 6 and 12 month follow-up	Changes in the WHOQOL-BREF score with respect to baseline value. It contains contains 26 questions each punctuated from 1 to 5 and assesses the individual's overall perception of quality of life (1 to 5), overall perception of their health (1 to 5) and 4 domains of physical health, psychological, social relationships, environment (0-100 each domain). higher scores denote higher quality of life.
AntiHLA antibodies in cerebrospinal fluid (CSF)	At 7 days and at 1 month follow-up after each infusion	Presence or absence of antiHLA antibodies in the CSF after two WJ-MSC infusions
Detection of donor cells in CSF	At 7 days after each infusion	Short tandem repeat (STR) analysis to detect permanence of donor cellularity (WJ-MsC) in the CSF

Trial Locations

Locations (2)

Complexo Hospitalario Universitario A Coruña (CHUAC); 🇪🇸 A Coruña, Spain

Hospital de Neurorehabilitació Institut Guttmann; 🇪🇸 Badalona, Barcelona, Spain