Clinical trial NCT05054803: Cell Therapy for Chronic Traumatic Cervical Incomplete Spinal Cord Injury
Official title: A Phase I/II, Randomized, Double-blind, Placebo-controlled, Parallel, 2-arms Clinical Trial to Assess the Safety and Efficacy of Intrathecal Administration of WJ-MSC in Chronic Traumatic Cervical Incomplete Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injury Cervical
Keywords: spinal cord injury
Mesenchymal stromal cells
Wharton jelly
Cell therapy
Lead sponsor: Banc de Sang i Teixits
Sponsor class: OTHER
Collaborators: name: Institut Guttmann
name: Academic Research Organization (ARO) - VHIR
name: Complexo Hospitalario Universitario de A Coruña
First posted: 2021-09-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized, placebo-controlled, 2-arms, multicenter clinical trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events
timeFrame: At 12 month follow-up
Secondary outcomes:
measure: American Spinal Injury Association (ASIA) impairment scale
timeFrame: At 1, 3, 4, 6 and 12 month follow-up
measure: Motor evoked potentials
timeFrame: At 6 and 12 month follow-up
measure: Somatosensory evoked potentials
timeFrame: At 6 and 12 month follow-up
measure: Electrical pain threshold perception
timeFrame: At 6 and 12 month follow-up
measure: Handgrip Strength
timeFrame: At 6 and 12 month follow-up
measure: Walking index for spinal cord injury (WISCI II)
timeFrame: At 6 and 12 month follow-up
measure: Numerical scale for neuropathic pain assessment
timeFrame: At 6 and 12 month follow-up
measure: Modified Ashworth scale for spasticity
timeFrame: At 6 and 12 month follow-up
measure: Spinal Cord Independence Measure III (SCIM III)
timeFrame: At 6 and 12 month follow-up
measure: World Health Organization Quality of life questionnaire (WHOQOL-BREF)
timeFrame: At 6 and 12 month follow-up
measure: Psychological general well-being index (PGWBI)
timeFrame: At 12 month follow-up
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: At 12 month follow-up
measure: Community Integration Questionaire (CIQ-IG)
timeFrame: At 12 month follow-up
measure: AntiHLA antibodies in cerebrospinal fluid (CSF)
timeFrame: At 7 days and at 1 month follow-up after each infusion
measure: Detection of donor cells in CSF
timeFrame: At 7 days after each infusion
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital de Neurorehabilitació Institut Guttmann
state: Barcelona
city: A Coruña
country: Spain
facility: Complexo Hospitalario Universitario A Coruña (CHUAC)
Study officials:
affiliation: 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.