Spinal Cord Injury, Acute
Conditions
Keywords
spinal cord injury, SCI, neurological deficit, stem cells, cell therapy, regenerative, paraplegia, tetraplegia
Brief summary
This is a prospective, single-blinded, single-center, randomized, comparative, interventional clinical study of systemic mononuclear multiple allogenic cord blood cells administration safety and efficiency in patients having acute severe contusion spinal cord injury (ASIA A/B), phase I/II
Detailed description
Phase I/II of the SUBSCI II (Systemic Umbilical Cord Blood Administration in Patients with Acute Severe Contusion Spinal Cord Injury II) study is focused on safety and primary efficacy of multiple systemic infusions of allogeneic unrelated human umbilical cord blood mononuclear cells in patients with severe acute spinal cord contusion having severe neurologic deficit (ASIA A/B). In a previous clinical study (SUBSCI I/IIa) complete safety and significant efficiency of systemic administration of human umbilical cord blood cells (HUCBCs) was demonstrated. Current study is established to confirm and verify the obtained results in a larger group of patients. SUBSCI II study includes 80 patients with acute severe contusion spinal cord injury (SCI) and American Spinal Injury Association (ASIA) level A/B deficit divided into 2 groups (experimental and control groups, 40 patients in each). Patients will be treated with 4 infusions of group-matched and rhesus-matched cord blood samples following primary decompressive and stabilizing surgery within 7 days after SCI. All patients will be followed up for 12 months after SCI.
Interventions
BIOLOGICALMultiple systemic (i.v.) administration of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
Each HUCBCs sample contain 500 +/- 50 x 10\*6 allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
OTHERControl vehicle (sterile saline)
Sterile saline infusion in control patients
Sponsors
State-Financed Health Facility Samara Regional Medical Center Dinasty
K.L. Hetagurov North-Osetian State University
Sklifosovsky Institute of Emergency Care
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
Participants in the experimental group will obtain 4 systemic (i.v.) infusions of allogenic group- and rhesus-compatible non-related mononuclear cord blood cell samples (500 +/- 50 x 10'6 cells each). Participants in the control group will obtain the similar volume of vehicle (sterile saline). Participant's devision will be performed in a randomized manner. Randomization will be performed using standard randomization computer table. All participants will be blinded concerning the therapy mode.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Both males and females, 18 to 75 years old * Contusion spinal cord injury (SCI) at cervical, thoracic or upper lumbar (cone level) levels * admission by 7 days post-SCI * spinal cord contusion confirmed using MRI (T1- and T2-weighted images, STIR) * ASIA A/B neurological deficit * identical level of neurological deficit at admission and at the moment of patient inclusion * primary decompressive and stabilizing surgery performed within 5 days post-SCI and prior to the first cell sample infused * patient is ready to participate and fulfill the requirements of the study protocol * informed consent signed by the patient or his legal representative
Exclusion criteria
* motor function preserved in lower limbs at admission (LEMS \> 0 points) corresponding to ASIA C, D or E deficit level * any spinal cord injury different from contusion (tear, defibering, concussion, SCIWORA, SCIWONA) confirmed using MRI * severe combined trauma (ISS \> 35 points) * inability to perform primary decompressive and stabilizing surgery within 5 days post-SCI and prior to the first cell sample infused * persistent systolic arterial pressure (AP) \> 185 mmHg or diastolic AP \> 105 mmHg or need of aggressive AP lowering using systemic antihypertensive medication at the moment of patient inclusion * acute myocardial infarction * blood glucose level \< 3.5 Mmol/L or \>21 Mmol/L or ineffective antidiabetic therapy for 24 hours * acute or deterioration of chronic diseases of central nervous system (CNS) (e.g. stroke, non-traumatic subarachnoid hemorrhages and others at the discretion of investigator) * hypotension or cardiovascular shock AND systolic AP \< 90 mmHg OR need for intensive systemic inotropic therapy at the moment of patient inclusion * objective need for artificial ling ventilation (ALV) at admission or prior to the stage I surgery * acute kidney failure or deterioration of chronic kidney failure (creatinin level \> 250 mumol/L or carbamide level \> 25 Mmol/L) * liver failure (general bilirubin level \> 25 mumol/L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels \> 4 times exceeding upper reference limit) * other significant disorders of vital functions * acute of deterioration of chronic diseases of internal organs preventing from cell samples infusion * autoimmune diseases (active or anamnestic) preventing from cell samples infusion * allergic reactions of any type for any component of HUCBC samples * pregnancy or lactation * significant surgeries or severe traumas within 3 months prior to patient inclusion * acute or chronic infection diseases (tuberculosis, lues, HIV, hepatitis B, hepatitis C etc.) * moderate or severe hematological and/or oncohematological diseases preventing from the cell samples infusion * any malignant tumors (both operated and not operated) or benign tumors (not operated or not totally removed) at the moment of patient inclusion * neurological and/or psychiatric diseases preventing patient from complete understanding of study protocol or fulfillment of the study protocol requirements * other reasons preventing patient from complete understanding of study protocol or fulfillment of the study protocol requirements * patient's participation in any other clinical trials or studies within 6 months prior to inclusion * immunosuppressive therapy obtained by the patient for any reason at admission * allergic reaction for full blood or blood component transfusion in the past * need for extracorporal detoxication methods application (hemodialysis, plasmapheresis, sorption etc.) * bone marrow or internal organs (both donor and relative) transplantation in the past * patient's participation in any studies applying regenerative technologies (grow factors, cytokines, cell therapy, gene therapy etc.) within 1 year prior to inclusion * patient's rejection to sign the informed consent * any other reasons preventing patient's inclusion according to the investigator's opinion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Continuously for 12 months post-SCI | All adverse events (AEs) are registered within follow-up period. All registered AEs are classified using CTCAE classification and relation to the performed therapy. |
| Motor function | Change from Baseline 12 months post-SCI | Evaluation of motor function dynamics in upper (UEMS), lower (LEMS) and all (GEMS) limbs |
| Neurological deficit | Change from Baseline 12 months post-SCI | Evaluation of general neurological deficit dynamics using ASIA scale |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Psychological status | Change from Baseline 12 months post-SCI | Evaluation of psychological status dynamics using Beck depression and anxiety scales and comparison between two groups |
| Sensory function | Change from Baseline 12 months post-SCI | Evaluation of pain, tactile, temperature and proprioceptive sensory function dynamics below SCI level and comparison between two groups |
| Pelvic functions | Change from Baseline 12 months post-SCI | Evaluation of pelvic functions dynamics (bladder fulfillment feeling, independent urination ability, urodynamic examination) |
| Neuropathic pain syndrome | 12 months post-SCI | Evaluation of neuropathic pain syndrome dynamics and comparison between two groups |
| Electrophysiology parameters | 12 months post-SCI | Assessment of electrophysiology objective parameters (electroneuromyography parameters with transcranial magnetic stimulation - full block, partial block or no block; somatosensory evoked potentials, motor evoked potentials) |
| Cell immunization | 12 months post-SCI | Assessment of patient's immunization to infused cell samples |
| Life quality | Change from Baseline 12 months post-SCI | Evaluation of life quality level in two groups using FIM (Functional Independence Measurement) scale and SF36 questionnaire |
| Independent verticalization and motion ability | Change from Baseline 12 months post-SCI | Evaluation of Independent verticalization and motion ability dynamics and comparison between two groups |
| Limb muscle spasticity | Change from Baseline 12 months post-SCI | Evaluation of limb muscle spasticity level dynamics using modified Ashworth or Tardieu scales and comparison between two groups |
Countries
Russia
Outcome results
None listed