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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04331405
Recruitment Status : Completed
First Posted : April 2, 2020
Last Update Posted : April 2, 2020
Sponsor:
Collaborator:
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
Information provided by (Responsible Party):
Vladimir A. Smirnov, Sklifosovsky Institute of Emergency Care

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.

Condition or disease Intervention/treatment Phase
Spinal Cord Contusion Biological: Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2013
Actual Primary Completion Date : March 21, 2018
Actual Study Completion Date : September 5, 2018

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Arm Intervention/treatment
Experimental: Pilot group
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.
Biological: Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions

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.


No Intervention: Control group
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.



Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety] [ Time Frame: 1 year ]

    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.


  2. Neurological Deficit Change [ASIA scale] [ Time Frame: Change from Baseline at 1 year after SCI ]
    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.

  3. Quality of Life [FIM scale] [ Time Frame: 1 year after SCI ]
    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 :
  1. Motor Deficit Change [Muscle Strength] [ Time Frame: Change from Baseline at 1 year after SCI ]

    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.


  2. Independent Verticalization Ability [ Time Frame: 1 year after SCI ]
    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.

  3. Lower Extremities Spasticity Level [Modified Asworth scale] [ Time Frame: 1 year after SCI ]
    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).

  4. Feeling of Bladder Filling [ Time Frame: 1 year after SCI ]
    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.

  5. Urinary Inconsistence [ Time Frame: 1 year after SCI ]
    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).

  6. Spinal Cord Conductivity [Electrophysiological assessment] [ Time Frame: 1 year after SCI ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04331405


Locations
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Russian Federation
N.V. Sklifosovsky Emergency Care Institute
Moscow, Russian Federation, 129090
Sponsors and Collaborators
Sklifosovsky Institute of Emergency Care
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
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Responsible Party: Vladimir A. Smirnov, MD, Sklifosovsky Institute of Emergency Care
ClinicalTrials.gov Identifier: NCT04331405    
Other Study ID Numbers: 41-18/03/2013
First Posted: April 2, 2020    Key Record Dates
Last Update Posted: April 2, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vladimir A. Smirnov, Sklifosovsky Institute of Emergency Care:
spinal cord injury
ASIA A/B
cell therapy
cord blood stem cells
regenerative medicine
Additional relevant MeSH terms:
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Spinal Cord Injuries
Contusions
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Wounds, Nonpenetrating