Spinal Cord ContusionPhase 1/2NCT04331405
Allogeneic Cord Blood Cells for Adults With Severe Acute Contusion Spinal Cord Injury
A Phase 1/2 study testing Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions in people with Spinal Cord Contusion, run by Sklifosovsky Institute of Emergency Care at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Spinal Cord Contusion
- What is being tested?
- Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteRussia
- Study dates
- 18 Mar 2013to 5 Sep 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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 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.
Read the 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.
- Conditions
- Spinal Cord Contusion
- Being tested
- Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions
- Keywords
- spinal cord injury, ASIA A/B, cell therapy, cord blood stem cells, regenerative medicine
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusionsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Pilot group | Experimental | 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. Receives: Biological: Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions |
| Control group | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
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.
Measured: Change from Baseline at 1 year after SCI
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.
Measured: 1 year after SCI
Secondary outcomes (6)
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.
Measured: Change from Baseline at 1 year after SCI
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.
Measured: 1 year after SCI
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).
Measured: 1 year after SCI
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.
Measured: 1 year after SCI
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).
Measured: 1 year after SCI
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).
Measured: 1 year after SCI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2020
- Study start18 Mar 2013
- Primary completion21 Mar 2018
- Study completion5 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord ContusionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sklifosovsky Institute of Emergency Care
- Sponsor type
- Other government
- Collaborators
- National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
- Responsible party
- Principal investigator, Vladimir A. Smirnov, Sklifosovsky Institute of Emergency Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04331405
- Sponsor's protocol ID
- 41-18/03/2013
- Status last verified
- Mar 2020
- First submitted
- 29 Mar 2020
- Last updated
- 2 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04331405
- Acronym / sponsor ID
- 41-18/03/2013
- Conditions
- Spinal Cord Contusion
- Keywords
- spinal cord injury, ASIA A/B, cell therapy, cord blood stem cells, regenerative medicine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Sklifosovsky Institute of Emergency CareOther government
- Collaborators
- National Medical Research Center for Cardiology, Ministry of Health of Russian Federation
- Study start
- 18 Mar 2013 (actual)
- Primary completion
- 21 Mar 2018 (actual)
- Study completion
- 5 Sep 2018 (actual)
- First posted
- 2 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Pilot group | Experimental | Biological: Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions10 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. |
| Control group | No intervention | –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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusionsHUCBMCs 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. | Biological | Pilot group |
Primary outcome
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.
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.
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.
6 secondary outcomes
Motor Deficit Change [Muscle Strength]
Time frame: Change from Baseline at 1 year after SCI
Independent Verticalization Ability
Time frame: 1 year after SCI
Lower Extremities Spasticity Level [Modified Asworth scale]
Time frame: 1 year after SCI
Feeling of Bladder Filling
Time frame: 1 year after SCI
Urinary Inconsistence
Time frame: 1 year after SCI
Spinal Cord Conductivity [Electrophysiological assessment]
Time frame: 1 year after SCI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
- Individual participant dataSharing planned: Undecided. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Human Allogeneic Umbilical Cord Blood Mononuclear Cells (hUCBMCs) systemic (i.v.) infusions in people with Spinal Cord Contusion, run by Sklifosovsky Institute of Emergency Care at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety] (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2020.