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Allogeneic Cord Blood Cells for Adults With Severe Acute Contusion Spinal Cord Injury

Primary Purpose

Spinal Cord Contusion

Status
Completed
Phase
Phase 1
Locations
Russian Federation
Study Type
Interventional
Intervention
Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions
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 Contusion focused on measuring spinal cord injury, ASIA A/B, cell therapy, cord blood stem cells, regenerative medicine

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • acute spinal cord injury (first 3 days after trauma)
  • contusion type of SCI (MRI-confirmed)
  • Russian citizenship
  • Informed consent understood and signed by the patient

Exclusion Criteria:

  • systolic arterial pressure (APsyst) > 185 mmHg OR diastolic AP (APdia) > 105 mmHg OR indications for aggressive AP lowering using i.v. therapy
  • myocardial infarction within 3 months prior to SCI
  • glucose level < 3.5 mM/L or > 21 mM/L
  • organic CNS pathology
  • acute internal organs diseases requiring surgical treatment
  • autoimmune diseases
  • serious surgical treatment or severe trauma within 3 months prior to SCI
  • pregnancy or breast feeding
  • acute infections including tuberculosis, syphilis, HIV, hepatitis B and C etc.
  • severe acute and chronic hematological diseases
  • rare patient's blood group parameters preventing adequate hUCBMCs sample selection (e.g. Kell+, A2B group, rare phenotype etc.)
  • any benign or oncological tumors (if not fully treated prior to SCI)
  • inability to participate in key examination following clinic discharge
  • any psychiatric diseases preventing patient from informed consent OR treatment plan understanding
  • confirmed hypersensitivity and/or allergy to any component of the studied biological compound
  • inability to accomplish present study protocol

Sites / Locations

  • N.V. Sklifosovsky Emergency Care Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Pilot group

Control group

Arm Description

10 patients with acute severe contusion spinal cord injury (ASIA A/B) included into the group. Patients meeting inclusion/exclusion criteria underwent primary surgical treatment (decompression and stabilization) received hUCBMC infusions weekly (4 infusions overall) in addition to standard therapy during in-hospital treatment. After the discharge patients were examined for 4 times. Observation period was 1 year.

10 patients with acute severe contusion spinal cord injury (ASIA A/B) included into the group. Patients meeting inclusion/exclusion criteria underwent primary surgical treatment (decompression and stabilization) received standard therapy during in-hospital treatment. After the discharge patients were examined for 4 times. Observation period was 1 year.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety]
All potential adverse events were analyzed during the first year after SCI. All adverse events (AEs) were classified using CTCAE v5.0 classification system in each of 10 patients of pilot group. Severity of AEs: Grade 1 - mild; asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 - moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL; Grade 3 - severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; Grade 4 - life-threatening consequences; urgent intervention indicated; Grade 5 - death related to AE. Relationship to the investigated therapy method: Degree 1 - unrelated; Degree 2 - possibly related; Degree 3 - probably related; Degree 4 - definitely related.
Neurological Deficit Change [ASIA scale]
Dynamics of neurological deficit level within 1 year after SCI was analyzed using ASIA clinical scale: ASIA A - total motor and sensory impairment; ASIA B - total motor impairment and partial sensory impairment below SCI level or pelvic sensitivity preserved; ASIA C - incomplete motor (at least half of key muscle strength less than 3 points) and sensory impairment; ASIA D - incomplete motor (at least half of key muscle strength more than 3 points) and sensory impairment; ASIA E - normal. Neurological deficit level was compared between pilot and control groups.
Quality of Life [FIM scale]
Quality of life level was assessed within 1 year after SCI using FIM (functional impairment) scale. FIM scale evaluates 5 groups of parameters including motor functions and self-service, mobility, motion level, pelvic functions and intellectual functions (e.g. communication and social activity). Each group includes several parameters assessed using point system (maximum 7 points for each parameter). A total sum of points is counted and compared between pilot and control groups.

Secondary Outcome Measures

Motor Deficit Change [Muscle Strength]
A dynamics of motor deficit was assessed using standard scale of key muscle strength. Two groups of parameters were considered including upper extremities strength (UEMS) and lower extremities strength (LEMS). Since patients with different SCI levels were included into the study (both cervical and thoracic/lumbar cone) LEMS parameter is more significant. Upper key muscles: C5 - biceps, С6 - wrist extensors, C7 - triceps, C8 - fingers flexors, Th1 - V finger abductor. Lower key muscles: L2 - m. psoas, L3 - quadriceps, L4 - m. tibialis anterior, L5 - I toe extensor, S1 - gastrocnemius. Both LEMS and cumulative (UEMS + LEMS) parameters were compared.
Independent Verticalization Ability
Patients ability to verticalize independently and mobility level were analyzed. First is determined by patient's ability to get up and stand more than 10 seconds without assistance. Second is determined by patient's ability to move without assistance depending on the distance: grade 1 - less than 10 m; grade 2 - less than 50 m; grade 3 - less than 100 m' grade 4 - 100 - 500 m; grade 5 - more than 500 m.
Lower Extremities Spasticity Level [Modified Asworth scale]
Spasticity level of lower extremities muscles was assessed using modified Ashworth scale. Grade 0 - no spasticity. Grade 1 - slight elevation of muscle tone, minimal tension at the end of movement amplitude during flexion and extension; Grade 1+ - slight elevation of muscle tone, minimal tension at least at half of movement amplitude. Grade 2 - moderate elevation of muscle tone during whole movement, but passive movements are not obstructed. Grade 3 - significant elevation of muscle tone, passive movements are partially obstructed. Grade 4 - rigid limb position in flexion or extension (contracture).
Feeling of Bladder Filling
Frequency of pelvic function disorders was assessed. Analysis included 2 parameters: (i) feeling of bladder filling and (ii) urinary inconsistence. First parameter is determined by patient's subjective feeling of bladder filling correlating to ultrasound confirmation of full bladder.
Urinary Inconsistence
Frequency of pelvic function disorders was assessed. Analysis included 2 parameters: (i) feeling of bladder filling and (ii) urinary inconsistence. Second parameter is determined by patient's ability for passive self-urination without application of any devices (e.g. urinary catheters, medical condoms or cystostomy).
Spinal Cord Conductivity [Electrophysiological assessment]
Spinal cord conductive function restoration was assessed using electrophysiological examination. Electroneuromyography supplemented with transcranial magnetic stimulation was performed to assess the level of signal conduction through the injured spinal cord. Significant diversity of SCI levels and baseline neurological deficit resulted in low significance of individual ENMG parameters comparison. Therefore only the parameters of conduction arrest was considered including (i) No conduction arrest (total or subtotal preservation of the overlay signal), (ii) Partial conduction arrest (decreased overlay signal) and (iii) Total conduction arrest (no overlay signal).

Full Information

First Posted
March 29, 2020
Last Updated
March 31, 2020
Sponsor
Sklifosovsky Institute of Emergency Care
Collaborators
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
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1. Study Identification

Unique Protocol Identification Number
NCT04331405
Brief Title
Allogeneic Cord Blood Cells for Adults With Severe Acute Contusion Spinal Cord Injury
Official Title
Allogeneic Mononuclear Umbilical Cord Blood Systemic Infusions for Adult Patients With Severe Acute Contusion Spinal Cord Injury: Phase I Safety Study and Phase IIa Primary Efficiency Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
March 18, 2013 (Actual)
Primary Completion Date
March 21, 2018 (Actual)
Study Completion Date
September 5, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sklifosovsky Institute of Emergency Care
Collaborators
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

4. Oversight

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

5. Study Description

Brief Summary
Study evaluates the safety and primary efficiency of systemic (i.v.) allogeneic human umbilical cord blood mononuclear cell infusions in patients with severe acute contusion spinal cord injury (ASIA A/B). 20 patients were included. Half of patients received cell therapy in addition to standard therapy, while the other half received standard therapy only.
Detailed Description
Present study was prospective randomized open-label clinical study, Phases I/IIa. Randomization was performed using envelope method (50 envelopes including Cell Therapy and Standard Therapy, 25 of each). 20 patients with severe scute contusion spinal cord injury (cervical, thoracic and lumbar cone segments) were included into the study. Patients were divided into 2 groups: pilot group (n = 10) obtaining standard conservative therapy and 4 i.v. infusions of Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) (~ 300 M in 100 mL) and control group (n = 10) obtaining standard conservative therapy only. Cell Therapy was initiated in patients within 3 days after SCI episode after primary surgical decompression and/or stabilization was performed. Patients inclusion decision depended on meeting the inclusion/exclusion criteria and informed consent signed. hUCBMC samples were prepared in the specialized laboratory and transported to the hospital immediately within 2 hours. Cells infusions were performed following 3 tests for biological compatibility and potential intolerance for each patient. All four infusion were performed during in-hospital treatment. Observational period reached 1 year after SCI. All included patients were examined daily during in-hospital treatment following 4 times within observational period (1 year). All adverse events and potential complications were analyzed within 1 year after SCI using CTCAE v5.0 classification. Outcome parameters were analyzed at the end of observation and examined using standard statistical instruments.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Contusion
Keywords
spinal cord injury, ASIA A/B, cell therapy, cord blood stem cells, regenerative medicine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
20 patients having acute contusion spinal cord injury (3 days post-trauma max) and ASIA A/B neurological deficit were divided into 2 groups: pilot group (n = 10) receiving hUCBMC treatment in addition to standard therapy and control group (n = 10) receiving standard treatment.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pilot group
Arm Type
Experimental
Arm Description
10 patients with acute severe contusion spinal cord injury (ASIA A/B) included into the group. Patients meeting inclusion/exclusion criteria underwent primary surgical treatment (decompression and stabilization) received hUCBMC infusions weekly (4 infusions overall) in addition to standard therapy during in-hospital treatment. After the discharge patients were examined for 4 times. Observation period was 1 year.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
10 patients with acute severe contusion spinal cord injury (ASIA A/B) included into the group. Patients meeting inclusion/exclusion criteria underwent primary surgical treatment (decompression and stabilization) received standard therapy during in-hospital treatment. After the discharge patients were examined for 4 times. Observation period was 1 year.
Intervention Type
Biological
Intervention Name(s)
Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions
Intervention Description
HUCBMCs samples were prepared for infusion in the specialized laboratory of Cord Blood Bank (CryoCenter Ltd) and transported to the clinic immediately within 2 hours in the Dry Shipper. All samples were chosen according to patients blood group and rhesus-factor. All samples were examined for hemotransmissive infections and cell viability prior to the preparation. Obtained samples were infused through the blood transfusion systems with additional filter after 3 tests for biological and individual compatibility and tolerance. Each patient of the pilot group received 4 cell infusions (1 infusion per week) with 1 week interval during the in-hospital treatment.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety]
Description
All potential adverse events were analyzed during the first year after SCI. All adverse events (AEs) were classified using CTCAE v5.0 classification system in each of 10 patients of pilot group. Severity of AEs: Grade 1 - mild; asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2 - moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL; Grade 3 - severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; Grade 4 - life-threatening consequences; urgent intervention indicated; Grade 5 - death related to AE. Relationship to the investigated therapy method: Degree 1 - unrelated; Degree 2 - possibly related; Degree 3 - probably related; Degree 4 - definitely related.
Time Frame
1 year
Title
Neurological Deficit Change [ASIA scale]
Description
Dynamics of neurological deficit level within 1 year after SCI was analyzed using ASIA clinical scale: ASIA A - total motor and sensory impairment; ASIA B - total motor impairment and partial sensory impairment below SCI level or pelvic sensitivity preserved; ASIA C - incomplete motor (at least half of key muscle strength less than 3 points) and sensory impairment; ASIA D - incomplete motor (at least half of key muscle strength more than 3 points) and sensory impairment; ASIA E - normal. Neurological deficit level was compared between pilot and control groups.
Time Frame
Change from Baseline at 1 year after SCI
Title
Quality of Life [FIM scale]
Description
Quality of life level was assessed within 1 year after SCI using FIM (functional impairment) scale. FIM scale evaluates 5 groups of parameters including motor functions and self-service, mobility, motion level, pelvic functions and intellectual functions (e.g. communication and social activity). Each group includes several parameters assessed using point system (maximum 7 points for each parameter). A total sum of points is counted and compared between pilot and control groups.
Time Frame
1 year after SCI
Secondary Outcome Measure Information:
Title
Motor Deficit Change [Muscle Strength]
Description
A dynamics of motor deficit was assessed using standard scale of key muscle strength. Two groups of parameters were considered including upper extremities strength (UEMS) and lower extremities strength (LEMS). Since patients with different SCI levels were included into the study (both cervical and thoracic/lumbar cone) LEMS parameter is more significant. Upper key muscles: C5 - biceps, С6 - wrist extensors, C7 - triceps, C8 - fingers flexors, Th1 - V finger abductor. Lower key muscles: L2 - m. psoas, L3 - quadriceps, L4 - m. tibialis anterior, L5 - I toe extensor, S1 - gastrocnemius. Both LEMS and cumulative (UEMS + LEMS) parameters were compared.
Time Frame
Change from Baseline at 1 year after SCI
Title
Independent Verticalization Ability
Description
Patients ability to verticalize independently and mobility level were analyzed. First is determined by patient's ability to get up and stand more than 10 seconds without assistance. Second is determined by patient's ability to move without assistance depending on the distance: grade 1 - less than 10 m; grade 2 - less than 50 m; grade 3 - less than 100 m' grade 4 - 100 - 500 m; grade 5 - more than 500 m.
Time Frame
1 year after SCI
Title
Lower Extremities Spasticity Level [Modified Asworth scale]
Description
Spasticity level of lower extremities muscles was assessed using modified Ashworth scale. Grade 0 - no spasticity. Grade 1 - slight elevation of muscle tone, minimal tension at the end of movement amplitude during flexion and extension; Grade 1+ - slight elevation of muscle tone, minimal tension at least at half of movement amplitude. Grade 2 - moderate elevation of muscle tone during whole movement, but passive movements are not obstructed. Grade 3 - significant elevation of muscle tone, passive movements are partially obstructed. Grade 4 - rigid limb position in flexion or extension (contracture).
Time Frame
1 year after SCI
Title
Feeling of Bladder Filling
Description
Frequency of pelvic function disorders was assessed. Analysis included 2 parameters: (i) feeling of bladder filling and (ii) urinary inconsistence. First parameter is determined by patient's subjective feeling of bladder filling correlating to ultrasound confirmation of full bladder.
Time Frame
1 year after SCI
Title
Urinary Inconsistence
Description
Frequency of pelvic function disorders was assessed. Analysis included 2 parameters: (i) feeling of bladder filling and (ii) urinary inconsistence. Second parameter is determined by patient's ability for passive self-urination without application of any devices (e.g. urinary catheters, medical condoms or cystostomy).
Time Frame
1 year after SCI
Title
Spinal Cord Conductivity [Electrophysiological assessment]
Description
Spinal cord conductive function restoration was assessed using electrophysiological examination. Electroneuromyography supplemented with transcranial magnetic stimulation was performed to assess the level of signal conduction through the injured spinal cord. Significant diversity of SCI levels and baseline neurological deficit resulted in low significance of individual ENMG parameters comparison. Therefore only the parameters of conduction arrest was considered including (i) No conduction arrest (total or subtotal preservation of the overlay signal), (ii) Partial conduction arrest (decreased overlay signal) and (iii) Total conduction arrest (no overlay signal).
Time Frame
1 year after SCI

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: acute spinal cord injury (first 3 days after trauma) contusion type of SCI (MRI-confirmed) Russian citizenship Informed consent understood and signed by the patient Exclusion Criteria: systolic arterial pressure (APsyst) > 185 mmHg OR diastolic AP (APdia) > 105 mmHg OR indications for aggressive AP lowering using i.v. therapy myocardial infarction within 3 months prior to SCI glucose level < 3.5 mM/L or > 21 mM/L organic CNS pathology acute internal organs diseases requiring surgical treatment autoimmune diseases serious surgical treatment or severe trauma within 3 months prior to SCI pregnancy or breast feeding acute infections including tuberculosis, syphilis, HIV, hepatitis B and C etc. severe acute and chronic hematological diseases rare patient's blood group parameters preventing adequate hUCBMCs sample selection (e.g. Kell+, A2B group, rare phenotype etc.) any benign or oncological tumors (if not fully treated prior to SCI) inability to participate in key examination following clinic discharge any psychiatric diseases preventing patient from informed consent OR treatment plan understanding confirmed hypersensitivity and/or allergy to any component of the studied biological compound inability to accomplish present study protocol
Facility Information:
Facility Name
N.V. Sklifosovsky Emergency Care Institute
City
Moscow
ZIP/Postal Code
129090
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
All the individual participant characteristics, assessed results of safety and efficiency evaluation, CT and MRI images can be provided to the interested persons and/or clinics via the contact with the Principal Investigator.

Learn more about this trial

Allogeneic Cord Blood Cells for Adults With Severe Acute Contusion Spinal Cord Injury

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