Cord Blood Cells in Patients With Acute SCI (SUBSCI II)

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

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

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injury, Acute
• Intervention / Treatment: Biological: Multiple systemic (i.v.) administration of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells; Other: Control vehicle (sterile saline)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 129090
    • Recruiting
    • N.V. Sklifosovsky Emergency Care Institute
    • Contact: Vladimir A. Smirnov, M.D., Ph.D.; Phone Number: +7-925-750-39-22; Email: vla_smirnov@mail.ru
    • Contact: Sergey E. Zuev, M.D.; Phone Number: +7-915-377-00-80; Email: zu85@bk.ru
    • Principal Investigator: Andrew A. Grin', Prof., M.D., Ph.D.
    • Principal Investigator: Vladimir A. Smirnov, M.D., Ph.D.
    • Sub-Investigator: Sergey E. Zuev, M.D.
    • Sub-Investigator: Alexander E. Talypov, M.D., Ph.D.
    • Sub-Investigator: Anton Yu. Kordonsky, M.D., Ph.D.
    • Sub-Investigator: Ivan S. Lvov, M.D., Ph.D.
    • Sub-Investigator: Yana V. Morozova, M.D., Ph.D.
    • Sub-Investigator: Sergey M. Radaev, M.D., Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cell Therapy; 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; Each HUCBCs sample contain 500 +/- 50 x 10*6 allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
Placebo Comparator: Vehicle; 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); Sterile saline infusion in control patients

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sklifosovsky Institute of Emergency Care
• Collaborators: State-Financed Health Facility "Samara Regional Medical Center Dinasty"; K.L. Hetagurov North-Osetian State University

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): August 30, 2025

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 12, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: stem cells; cell therapy; spinal cord injury; SCI; tetraplegia; regenerative; paraplegia; neurological deficit
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: 007-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Personal contacts via E-mail or phone after the completion of the study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No