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

March 31, 2020 updated by: Vladimir A. Smirnov, Sklifosovsky Institute of Emergency Care

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 129090
        • N.V. Sklifosovsky Emergency Care Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
1 year
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.
Change from Baseline at 1 year after SCI
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.
1 year after SCI

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Change from Baseline at 1 year after SCI
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.
1 year after SCI
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).
1 year after SCI
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.
1 year after SCI
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).
1 year after SCI
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).
1 year after SCI

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sklifosovsky Institute of Emergency Care

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Medical Research Center for Cardiology, Ministry of Health of Russian Federation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 18, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 21, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 5, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 29, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 2, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 2, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 31, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 41-18/03/2013

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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