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

Primary Purpose

Spinal Cord Injury, Acute

Status
Recruiting
Phase
Phase 1
Locations
Russian Federation
Study Type
Interventional
Intervention
Multiple systemic (i.v.) administration of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
Control vehicle (sterile saline)
Sponsored by
Sklifosovsky Institute of Emergency Care
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injury, Acute focused on measuring spinal cord injury, SCI, neurological deficit, stem cells, cell therapy, regenerative, paraplegia, tetraplegia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • N.V. Sklifosovsky Emergency Care InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cell Therapy

Vehicle

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.
Motor function
Evaluation of motor function dynamics in upper (UEMS), lower (LEMS) and all (GEMS) limbs
Neurological deficit
Evaluation of general neurological deficit dynamics using ASIA scale

Secondary Outcome Measures

Sensory function
Evaluation of pain, tactile, temperature and proprioceptive sensory function dynamics below SCI level and comparison between two groups
Neuropathic pain syndrome
Evaluation of neuropathic pain syndrome dynamics and comparison between two groups
Independent verticalization and motion ability
Evaluation of Independent verticalization and motion ability dynamics and comparison between two groups
Limb muscle spasticity
Evaluation of limb muscle spasticity level dynamics using modified Ashworth or Tardieu scales and comparison between two groups
Psychological status
Evaluation of psychological status dynamics using Beck depression and anxiety scales and comparison between two groups
Pelvic functions
Evaluation of pelvic functions dynamics (bladder fulfillment feeling, independent urination ability, urodynamic examination)
Life quality
Evaluation of life quality level in two groups using FIM (Functional Independence Measurement) scale and SF36 questionnaire
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)
Cell immunization
Assessment of patient's immunization to infused cell samples

Full Information

First Posted
November 21, 2022
Last Updated
January 12, 2023
Sponsor
Sklifosovsky Institute of Emergency Care
Collaborators
State-Financed Health Facility "Samara Regional Medical Center Dinasty", K.L. Hetagurov North-Osetian State University
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1. Study Identification

Unique Protocol Identification Number
NCT05693181
Brief Title
Cord Blood Cells in Patients With Acute SCI
Acronym
SUBSCI II
Official Title
Systemic Administration of Allogenic Mononuclear Cord Blood Cells in Patients With Acute Severe Contusion Spinal Cord Injury: Safety and Efficiency Evaluation, Stages I/II
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 5, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
August 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sklifosovsky Institute of Emergency Care
Collaborators
State-Financed Health Facility "Samara Regional Medical Center Dinasty", K.L. Hetagurov North-Osetian State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury, Acute
Keywords
spinal cord injury, SCI, neurological deficit, stem cells, cell therapy, regenerative, paraplegia, tetraplegia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
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.
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cell Therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Vehicle
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Multiple systemic (i.v.) administration of allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
Intervention Description
Each HUCBCs sample contain 500 +/- 50 x 10*6 allogenic non-related group- and rhesus-compatible mononuclear cord blood cells
Intervention Type
Other
Intervention Name(s)
Control vehicle (sterile saline)
Intervention Description
Sterile saline infusion in control patients
Primary Outcome Measure Information:
Title
Adverse events
Description
All adverse events (AEs) are registered within follow-up period. All registered AEs are classified using CTCAE classification and relation to the performed therapy.
Time Frame
Continuously for 12 months post-SCI
Title
Motor function
Description
Evaluation of motor function dynamics in upper (UEMS), lower (LEMS) and all (GEMS) limbs
Time Frame
Change from Baseline 12 months post-SCI
Title
Neurological deficit
Description
Evaluation of general neurological deficit dynamics using ASIA scale
Time Frame
Change from Baseline 12 months post-SCI
Secondary Outcome Measure Information:
Title
Sensory function
Description
Evaluation of pain, tactile, temperature and proprioceptive sensory function dynamics below SCI level and comparison between two groups
Time Frame
Change from Baseline 12 months post-SCI
Title
Neuropathic pain syndrome
Description
Evaluation of neuropathic pain syndrome dynamics and comparison between two groups
Time Frame
12 months post-SCI
Title
Independent verticalization and motion ability
Description
Evaluation of Independent verticalization and motion ability dynamics and comparison between two groups
Time Frame
Change from Baseline 12 months post-SCI
Title
Limb muscle spasticity
Description
Evaluation of limb muscle spasticity level dynamics using modified Ashworth or Tardieu scales and comparison between two groups
Time Frame
Change from Baseline 12 months post-SCI
Title
Psychological status
Description
Evaluation of psychological status dynamics using Beck depression and anxiety scales and comparison between two groups
Time Frame
Change from Baseline 12 months post-SCI
Title
Pelvic functions
Description
Evaluation of pelvic functions dynamics (bladder fulfillment feeling, independent urination ability, urodynamic examination)
Time Frame
Change from Baseline 12 months post-SCI
Title
Life quality
Description
Evaluation of life quality level in two groups using FIM (Functional Independence Measurement) scale and SF36 questionnaire
Time Frame
Change from Baseline 12 months post-SCI
Title
Electrophysiology parameters
Description
Assessment of electrophysiology objective parameters (electroneuromyography parameters with transcranial magnetic stimulation - full block, partial block or no block; somatosensory evoked potentials, motor evoked potentials)
Time Frame
12 months post-SCI
Title
Cell immunization
Description
Assessment of patient's immunization to infused cell samples
Time Frame
12 months post-SCI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
N.V. Sklifosovsky Emergency Care Institute
City
Moscow
ZIP/Postal Code
129090
Country
Russian Federation
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vladimir A. Smirnov, M.D., Ph.D.
Phone
+7-925-750-39-22
Email
vla_smirnov@mail.ru
First Name & Middle Initial & Last Name & Degree
Sergey E. Zuev, M.D.
Phone
+7-915-377-00-80
Email
zu85@bk.ru
First Name & Middle Initial & Last Name & Degree
Andrew A. Grin', Prof., M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Vladimir A. Smirnov, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Sergey E. Zuev, M.D.
First Name & Middle Initial & Last Name & Degree
Alexander E. Talypov, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Anton Yu. Kordonsky, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Ivan S. Lvov, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Yana V. Morozova, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Sergey M. Radaev, M.D., Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Personal contacts via E-mail or phone after the completion of the study

Learn more about this trial

Cord Blood Cells in Patients With Acute SCI

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