Cord Blood Cells in Patients With Acute SCI

Study Overview
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Brief Summary
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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
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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.

Official Title
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Systemic Administration of Allogenic Mononuclear Cord Blood Cells in Patients With Acute Severe Contusion Spinal Cord Injury: Safety and Efficiency Evaluation, Stages I/II

Conditions
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Spinal Cord Injury, Acute

Intervention / Treatment
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* Biological: Multiple systemic (i.v.) administration of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
* Other: Control vehicle (sterile saline)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cell Therapy<br>Patients having acute severe contusion spinal cord injury (cervical, thoracic or upper-lumbar) and ASIA A/B neurological deficit, within 7 days post-SCI, after primary decompressive and stabilizing surgery. All participants meet inclusion and exclusion criteria. All participants obtain 4 infusions of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells samples (500 +/- 50 x 10*6 cells each) with a 1-week interval. All participants are followed up for 12 months post-SCI. | Biological: Multiple systemic (i.v.) administration of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells<br>* Each HUCBCs sample contain 500 +/- 50 x 10*6 allogenic non-related group- and rhesus-compatible mononuclear cord blood cells<br>|
| Placebo Comparator: Vehicle<br>Patients having acute severe contusion spinal cord injury (cervical, thoracic or upper-lumbar) and ASIA A/B neurological deficit, within 7 days post-SCI, after primary decompressive and stabilizing surgery. All participants meet inclusion and exclusion criteria. All participants obtain 4 infusions of vehicle (sterile saline) with a 1-week interval. All participants are followed up for 12 months post-SCI. | Other: Control vehicle (sterile saline)<br>* Sterile saline infusion in control patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | All adverse events (AEs) are registered within follow-up period. All registered AEs are classified using CTCAE classification and relation to the performed therapy. | Continuously for 12 months post-SCI | 
| Motor function | Evaluation of motor function dynamics in upper (UEMS), lower (LEMS) and all (GEMS) limbs | Change from Baseline 12 months post-SCI | 
| Neurological deficit | Evaluation of general neurological deficit dynamics using ASIA scale | Change from Baseline 12 months post-SCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensory function | Evaluation of pain, tactile, temperature and proprioceptive sensory function dynamics below SCI level and comparison between two groups | Change from Baseline 12 months post-SCI | 
| Neuropathic pain syndrome | Evaluation of neuropathic pain syndrome dynamics and comparison between two groups | 12 months post-SCI | 
| Independent verticalization and motion ability | Evaluation of Independent verticalization and motion ability dynamics and comparison between two groups | Change from Baseline 12 months post-SCI | 
| Limb muscle spasticity | Evaluation of limb muscle spasticity level dynamics using modified Ashworth or Tardieu scales and comparison between two groups | Change from Baseline 12 months post-SCI | 
| Psychological status | Evaluation of psychological status dynamics using Beck depression and anxiety scales and comparison between two groups | Change from Baseline 12 months post-SCI | 
| Pelvic functions | Evaluation of pelvic functions dynamics (bladder fulfillment feeling, independent urination ability, urodynamic examination) | Change from Baseline 12 months post-SCI | 
| Life quality | Evaluation of life quality level in two groups using FIM (Functional Independence Measurement) scale and SF36 questionnaire | Change from Baseline 12 months post-SCI | 
| Electrophysiology parameters | Assessment of electrophysiology objective parameters (electroneuromyography parameters with transcranial magnetic stimulation - full block, partial block or no block; somatosensory evoked potentials, motor evoked potentials) | 12 months post-SCI | 
| Cell immunization | Assessment of patient's immunization to infused cell samples | 12 months post-SCI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCI, regenerative, spinal cord injury, neurological deficit, stem cells, cell therapy, paraplegia, tetraplegia