Spinal Cord Disease, Spinal Cord Injuries (SCI), Spinal Cord Injury, Traumatic Spinal Cord Injuries
Conditions
Keywords
Mesenchymal Stem Cells, Spinal Cord Injuries, Cell- and Tissue-Based Therapy, Intrathecal Administration, Neuroplasticity, Spinal Cord Stimulation, Safety, Clinical Trials, Phase I, Electric Stimulation Therapy, Feasibility Study
Brief summary
This clinical trial primarily aims to evaluate the safety and feasibility of a combined therapeutic approach for chronic spinal cord injury (SCI). The study will investigate whether the combination of intrathecal Wharton's jelly mesenchymal stem cells and transcutaneous spinal cord stimulation (tSCS) is safe and viable in individuals with chronic traumatic SCI. The trial will enrol 10 participants aged 16-70 with traumatic SCI (cervical or thoracic levels C1-T12) classified as ASIA Impairment Scale A-C, who are 1-5 years post-injury. Participants will receive three intrathecal injections of Wharton's jelly mesenchymal stem cells, each containing 30 million viable cells (±30%), administered intrathecally at the L3-L4 level. This cellular therapy will be combined with transcutaneous spinal cord stimulation and intensive neurorehabilitation. Participants will undergo comprehensive assessments over a 12-month follow-up period to monitor safety, feasibility, and secondarily to evaluate potential improvements in motor, sensory, and autonomic functions. Additional annual follow-up will continue for 2 years after study completion to evaluate long-term safety.
Interventions
COMBINATION_PRODUCTAllogeneic Wharton's jelly mesenchymal stem cells (WJ-MSCs)
This experimental treatment combines intrathecal administration of allogeneic Wharton's jelly mesenchymal stem cells (WJ-MSCs) with transcutaneous spinal cord stimulation (tSCS) and neurorehabilitation. Participants will receive three doses of cryopreserved WJ-MSCs (30×10⁶±30% viable cells per dose) derived from umbilical cord tissue, delivered via lumbar puncture at 6-week intervals in a saline-albumin solution. The intervention includes concurrent tSCS, a non-invasive electrical stimulation technique, paired with standardised neurorehabilitation. As the first clinical study evaluating this specific combined therapy for chronic spinal cord injury (AIS A-C grades), safety monitoring incorporates regular cerebrospinal fluid analysis to assess potential immune responses.
Sponsors
Institut Guttmann
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This single-arm, open-label pilot study combines intrathecal Wharton's jelly mesenchymal stem cells (3 doses of 30×10⁶±30% cells at 6week-intervals) with transcutaneous spinal cord stimulation (tSCS) in chronic SCI patients (AIS A-C, 1-5 years post-injury). The model evaluates: * Safety (AEs, neurological/immunological monitoring) * Feasibility (adherence/retention rates) * Efficacy signals (motor/sensory/autonomic improvements via ASIA, neurophysiological tests). * All participants receive active treatment with 12-month core follow-up + 2-year extended safety monitoring.
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Individuals aged 16-70 years (parental consent required for 16-18-year-olds) * Single traumatic spinal cord injury (AIS A-C) at C1-T12 levels * Chronic injury (1-5 years post-injury) * Stable medical condition with life expectancy \>2 years * Ability to attend follow-up visits and comply with all study procedures * Written informed consent (and parental consent for minors) * Sufficient cognitive capacity to understand the study * For women of childbearing potential: use of effective contraception (hormonal, intrauterine device, barrier methods, sterilization, or post-menopausal status \>1 year)
Exclusion criteria
* Severe comorbidities (e.g., cardiovascular instability, active infections) * Individuals requiring mechanical ventilation * Contraindications for tSCS (e.g., implanted devices) * Pregnancy or breastfeeding * Neurodegenerative diseases * Significant haematological/biochemical abnormalities * Active or recent (≤5 years) malignancy without complete remission * Positive serology for HIV, hepatitis B virus, hepatitis C virus, or syphilis * Communication barriers (language, aphasia) * Concurrent participation in another clinical trial (within 30 days) * Recent intrathecal medication or immunosuppressants (within 60 days) * Multi-level spinal lesions or lesions \>3 spinal segments on MRI * Contraindications for lumbar puncture * Planned spinal surgery within 24 months * Inability to participate in rehabilitation * Known allergies to stem cell preparation components
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) in Chronic SCI | Baseline through Month 12 post-treatment | Safety assessment evaluating: 1. Neurological worsening (≥1-grade decline on the American Spinal Injury Association (ASIA) Impairment Scale \[AIS\], grades A-E, where higher grades indicate better function). 2. Cerebrospinal fluid (CSF) abnormalities (e.g., pleocytosis, elevated protein). 3. Procedure-related complications (e.g., post-lumbar puncture headache, infection). Unit of Measure: Composite binary outcome (presence/absence of any TEAE). |
| Protocol Adherence Rate for Combined WJ-MSCs and tSCS Therapy | From baseline to week 18. | Feasibility assessment measuring adherence to: 1. Scheduled intrathecal WJ-MSC administrations (3 doses at 6-week intervals). 2. Concomitant tSCS-assisted neurorehabilitation sessions (18 weeks). Unit of Measure: Percentage of completed interventions vs. planned (%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in American Spinal Injury Association (ASIA) Impairment Scale [AIS] Pinprick Sensory Score | Baseline to Month 12. | Change in pinprick sensation measured by the American Spinal Injury Association (ASIA) Impairment Scale \[AIS\] Pinprick Sensory Score (0-112 points, tested across 28 dermatomes). Higher scores indicate better sensory function. Unit of Measure: Points on American Spinal Injury Association (ASIA) Impairment Scale \[AIS\] Pinprick Scale. |
| Change in Autonomic Control | Baseline to Month 12. | Change in autonomic function (e.g., bladder, bowel, cardiovascular regulation) assessed using the International Standards to document Autonomic Function after Spinal Cord Injury (ISAFSCI). Scores range from 0 (no function) to 2 (normal function) per domain. Higher scores indicate better autonomic control. Unit of Measure: Autonomic Function after Spinal Cord Injury (ISAFSCI) composite score. |
| Change in Motor Evoked Potential (MEP) Amplitude | Baseline to Month 12. | Change in corticospinal tract integrity measured by Motor Evoked Potential (MEP) amplitude during transcranial magnetic stimulation. In the absence of pathological hyperexcitability, higher MEP amplitudes generally reflect better corticospinal tract integrity. Unit of Measure: Microvolts (µV). |
| Change in American Spinal Injury Association (ASIA) Impairment Scale [AIS] Motor Score | Baseline to Month 12 | Change in motor function measured by the American Spinal Injury Association (ASIA) Impairment Scale \[AIS\] Motor Score, which evaluates voluntary muscle strength across 10 key muscle groups (0-5 points per muscle, total range 0-100). Higher scores indicate better motor function. Unit of Measure: Points on American Spinal Injury Association (ASIA) Impairment Scale \[AIS\] Motor Scale. |
| Change in Somatosensory Evoked Potential (SSEP) Amplitude | Baseline to Month 12. | Change in dorsal column-medial lemniscus pathway integrity measured by Somatosensory Evoked Potential (SSEP) amplitude during peripheral nerve stimulation. In the absence of pathological hyperexcitability, higher SSEP amplitudes generally reflect better somatosensory pathway integrity. Unit of Measure: Microvolts (µV). |
| Change in Somatosensory Evoked Potential (SSEP) Latency | Baseline to Month 12. | Change in somatosensory pathway conduction speed measured by Somatosensory Evoked Potential (SSEP) latency during peripheral nerve stimulation. Shorter latencies generally reflect faster, more efficient conduction along the dorsal column-medial lemniscus pathway. Unit of Measure: Milliseconds (ms). |
| Change in Motor Evoked Potential (MEP) Latency | Baseline to Month 12. | Change in corticospinal conduction speed measured by Motor Evoked Potential (MEP) latency during transcranial magnetic stimulation. Shorter latencies generally reflect faster, more efficient corticospinal tract conduction. Unit of Measure: Milliseconds (ms). |
| Change in American Spinal Injury Association (ASIA) Impairment Scale [AIS] Light Touch Sensory Score | Baseline to Month 12. | Change in light touch sensation measured by the American Spinal Injury Association (ASIA) Impairment Scale \[AIS\] Light Touch Sensory Score (0-112 points, tested across 28 dermatomes). Higher scores indicate better sensory function. Unit of Measure: Points on American Spinal Injury Association (ASIA) Impairment Scale \[AIS\] Light Touch Scale. |
Countries
Spain
Contacts
Primary ContactJoan Vidal Samsó, MD, PhD
Backup ContactFernando Martins Braga, MD, MSc
Outcome results
None listed