Spinal Cord InjuryPhase 1CME-LEM1NCT01909154
Safety Study of Local Administration of Autologous Bone Marrow Stromal Cells in Chronic Paraplegia
A Phase 1 study testing Mesenchymal stromal cell therapy in people with Spinal Cord Injury, run by Puerta de Hierro University Hospital at 1 site in Spain.
Trial summary
The purpose of this study is to confirm the security, and detect the effect of the local administration in damaged nervous tissue, of autologous bone marrow stromal cells. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- Mesenchymal stromal cell therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSpain
- Study dates
- Mar 2013to Mar 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female with ages between 18 years and 60 years with of age or older functional sequelae chronically established by traumatic injury of the spinal cord (spinal segments between the vertebral bodies C6 and L1) and considered irreversible (not respond to any other treatment). In this study, the lesion is considered chronically established, when there are no signs of functional recovery after a minimum follow-up period of 6 months after the spinal cord injury. The upper age limit is justified by the low potential of in vitro expansion of bone marrow stromal cells over 60 years.
- Complete paraplegia, with loss of motor and sensory function below the lesion (grade A in the American Spinal Injury Association Impairment (ASIA) Scale .
- Spinal injury MRI morphologically visible, and without images that suggest spinal cord transection, with separation of the both ends of the spinal cord.
- Tracking evolutionary possibility after treatment protocol and to comply physiotherapy maintained throughout the follow up period.
- Written informed Consent according to good clinical practice (GCP) and local regulations, obtained before any study procedure.
- Hematological parameters and creatinine, serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) in normal range according to laboratory standards, are accepted, however, small non-significant deviations according to the investigator.
Who cannot join
- Pregnancy and lactation
- Systemic disease represents an added risk to treatment
- Patients with questions about their possible cooperation in rehabilitation-physiotherapy treatments later, or negative report psychological assessment prior.
- Neuroimaging data showing spinal cord section with separation of the terminal portion of the spinal cord
- Current neoplastic disease diagnosed or treated in the previous five years
- Patients treated with hematopoietic growth factors or requiring stable anticoagulation
Show all 10Show fewer
- Added neurodegenerative disease
- History of substance abuse, psychiatric illness or allergy to protein products used in the process of cell expansion
- HIV positive serology and syphilis
- Hepatitis B or Hepatitis C active According to the investigator's opinion if there are findings on physical examination, abnormal clinical test results or other medica relevant entries, social or psychosocial factors which might influence negatively the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Pilot Study to Evaluate the Security of Local Administration of Autologous Stem Cells Obtained From the Bone Marrow Stroma, in Traumatic Injuries of the Spinal Cord
The purpose of this study is to confirm the security, and detect the effect of the local administration in damaged nervous tissue, of autologous bone marrow stromal cells.
Read the detailed description
It is a clinical trial phase I, single center, non-randomized, uncontrolled, open prospective follow-up of a cohort of patients with chronic spinal cord injury (SCI) who were treated with autologous stromal cells of the bone marrow administrated locally (subarachnoid and intramedullar) by intrathecal microinjection and three months later, by lumbar subarachnoid administration. The minimum follow-up duration for each patient is 12 months after the first administration, or until death, if it occurs it before.
- Conditions
- Spinal Cord Injury
- Being tested
- Mesenchymal stromal cell therapy
- Keywords
- neurophysiological parameters improvement, spinal cord injury, biology therapy
- 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.
Mesenchymal stromal cell therapyBiological
Also called BMMSCs= Bone Marrow Mesenchymal Stem Cells
Stem cells administration locally
| Study group | Role | What they receive |
|---|---|---|
| Mesenchymal stromal cell therapy | Experimental | Autologous bone marrow adult mesenchymal stem cells expanded in vitro. Administered by Intrathecal injection (subarachnoid and intramedullary). Depending on centromedullary post-traumatic injury: bone marrow stromal stem cells administration (MSCs) at the minimum dose of 100x106 followed by subarachnoid administration of 30x106 MSCs,3 months later Receives: Biological: Mesenchymal stromal cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety-Number of Adverse Events
Clinical evaluation of possible adverse effects is performed daily at the first week after the first administration of stem cells and weekly until the 6 months follow-up visit and then at month 9 and 12. .
- During the first stem cells administration (during surgery): Changes in vital signs (ECG, Blood Pressure (BP), Heart Rate (HR) were evaluated
- During the second stem cells administration: Changes in vital signs (BP, HR), headache and meningeal irritation were evaluated
- During the first weeks, after the first and the second administrations, the possibility of meningeal irritation, headache and infectious complications were considerate.
MedDRA stardards are followed
Measured: Up to 12 months
Secondary outcomes (5)
Efficacy-Sensitivity Recovery Using ASIA Scale
Sensitivity recovery was measured using the ASIA (American Spinal Injury Association) scale to measure the Surface sensitivity (LTS), pain sensitivity (PPS), and the degree of motor function in key muscles (MS). The sum of MS, LTS, and PPS configure total ASIA score. A minimum possible score is 0 points. A maximum possible score is 224 points for a patient with normal sensation.
ASIA score was obtained before surgery, and 3, 6, 9 and 12 months after surgery. Mean and standard deviation for the 12 patients were obtained at all the time points and statistically analyzed.
Measured: sensitivity before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
Changes in the level of chronic pain, measured by the pain section of the IANR-SCIFRS (Spinal cord injury functional rating scale (SCI-FRS) of the international association of neuroestoratology (IANR). The minimum posible score is 0, and the máximum posible score is 48, being a score of 48 a normal functioning across all categories, and 0 a severe degree of functional hándicap (significant impact of daily life).
Pain is classified as no pain; mild pain, ordinary pain killer, effective;severe pain, narcotics required; extreme pain, uncontrolled.
Measured: Changes in the level of Chronic pain before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Efficacy- Changes in the Neurophysiological Parameters Measured as the Number of Patients With SSEPs (Somatosensory Evoked Potentials)
Changes in the neurophysiological parameters (SSEPs, somatosensory evoked potentials) measured as number of patients WITH SSEPs, each patient through underwent neurophysiological studies before treatment, as well as six and 12 months after surgery, paying attention mainly to the presence or abscence of somatosensory evoked potentials (SSEPs), the presence or absence of motor evoked potentials (MEPs) elicited by magnetic stimulation over the scalp, and to electromyographic (EMG) recording of motor unit potentials in infralesional muscles. Previous to cell therapy in any of the patients SSEPs were recorded.
Measured: Changes in the level neurophysiological parameters improvement (baseline visit) and 6, 12 months after surgery (follow-up period)
Efficacy-Urodynamic Studies in Terms of máximum Cystometric Capacity
Urodynamic studies in terms of voluntary micturition in flowmetry or in pressure/flow test, increase in bladder compliance. detrusor pressure (decrease on detrusor pressure is considered a clinical improvement). The neurogenic bladder is one of the biggest problems associated with SCI (spinal cord injury), with important personal and social implications.
Measured: Urodynamic studies before surgery and 12 months after surgery (follow-up period)
Efficacy-modification of Magnetic Resonance Imaging (MRI)
Number of patients with a decrease in volume and hyperintensity of intramedullary lesions. In general, in the areas of SCI, variable degree of spinal cord atrophy and hiperintense images are observed. These images corresponds to cysts, gliosis and myelomalacia. After cell administration a reduction of supposed cyst and a decrease or disappearance of hyperintense lesions suggest a patient improvement.
Measured: changes in the spinal cord morphology on neuroimaging studies before surgery and 12 months after surgery (follow-up period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2013 (estimated)
- Study startMar 2013
- Primary completionApr 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord InjuryStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Puerta de Hierro University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jesús Vaquero Crespo, M.D., Puerta de Hierro University Hospital
- Investigators
- Jesus JV Vaquero Crespo, Dr., Principal investigator, Hospital Universitario Puerta de Hierro Majadahonda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01909154
- Sponsor's protocol ID
- CME-LEM1
- Other IDs
- 2010-023285-46
- Acronym
- CME-LEM1
- Status last verified
- Mar 2019
- First submitted
- 7 Jul 2013
- Last updated
- 29 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: nonymized individual data of participants will be shared with Authorities at the end of the Clinical Development Plan by the CTD (Common Technical Document). Results will be published in a scientific publication.
Publications
Geffner LF, Santacruz P, Izurieta M, Flor L, Maldonado B, Auad AH, Montenegro X, Gonzalez R, Silva F. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant. 2008;17(12):1277-93. doi: 10.3727/096368908787648074.
PubMed 19364066
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Pilot Study to Evaluate the Security of Local Administration of Autologous Stem Cells Obtained From the Bone Marrow Stroma, in Traumatic Injuries of the Spinal Cord
- ClinicalTrials.gov ID
- NCT01909154
- Acronym / sponsor ID
- CME-LEM1 / CME-LEM1
- Conditions
- Spinal Cord Injury
- Keywords
- neurophysiological parameters improvement, spinal cord injury, biology therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Puerta de Hierro University HospitalUniversity, hospital or other
- Study start
- Mar 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 26 Jul 2013 (estimated)
- Results
- Posted 29 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to confirm the security, and detect the effect of the local administration in damaged nervous tissue, of autologous bone marrow stromal cells.
Detailed description
It is a clinical trial phase I, single center, non-randomized, uncontrolled, open prospective follow-up of a cohort of patients with chronic spinal cord injury (SCI) who were treated with autologous stromal cells of the bone marrow administrated locally (subarachnoid and intramedullar) by intrathecal microinjection and three months later, by lumbar subarachnoid administration. The minimum follow-up duration for each patient is 12 months after the first administration, or until death, if it occurs it before.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal stromal cell therapy | Experimental | Biological: Mesenchymal stromal cell therapyAutologous bone marrow adult mesenchymal stem cells expanded in vitro. Administered by Intrathecal injection (subarachnoid and intramedullary). Depending on centromedullary post-traumatic injury: bone marrow stromal stem cells administration (MSCs) at the minimum dose of 100x106 followed by subarachnoid administration of 30x106 MSCs,3 months later |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Male or female with ages between 18 years and 60 years with of age or older functional sequelae chronically established by traumatic injury of the spinal cord (spinal segments between the vertebral bodies C6 and L1) and considered irreversible (not respond to any other treatment). In this study, the lesion is considered chronically established, when there are no signs of functional recovery after a minimum follow-up period of 6 months after the spinal cord injury. The upper age limit is justified by the low potential of in vitro expansion of bone marrow stromal cells over 60 years.
- Complete paraplegia, with loss of motor and sensory function below the lesion (grade A in the American Spinal Injury Association Impairment (ASIA) Scale .
- Spinal injury MRI morphologically visible, and without images that suggest spinal cord transection, with separation of the both ends of the spinal cord.
- Tracking evolutionary possibility after treatment protocol and to comply physiotherapy maintained throughout the follow up period.
- Written informed Consent according to good clinical practice (GCP) and local regulations, obtained before any study procedure.
Key exclusion criteria (10 listed)
- Pregnancy and lactation
- Systemic disease represents an added risk to treatment
- Patients with questions about their possible cooperation in rehabilitation-physiotherapy treatments later, or negative report psychological assessment prior.
- Neuroimaging data showing spinal cord section with separation of the terminal portion of the spinal cord
- Current neoplastic disease diagnosed or treated in the previous five years
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 |
|---|---|---|
| Mesenchymal stromal cell therapyAlso: BMMSCs= Bone Marrow Mesenchymal Stem CellsStem cells administration locally | Biological | Mesenchymal stromal cell therapy |
Primary outcome
Safety-Number of Adverse Events
Time frame: Up to 12 months
Clinical evaluation of possible adverse effects is performed daily at the first week after the first administration of stem cells and weekly until the 6 months follow-up visit and then at month 9 and 12. . * During the first stem cells administration (during surgery): Changes in vital signs (ECG, Blood Pressure (BP), Heart Rate (HR) were evaluated * During the second stem cells administration: Changes in vital signs (BP, HR), headache and meningeal irritation were evaluated * During the first weeks, after the first and the second administrations, the possibility of meningeal irritation, headache and infectious complications were considerate. MedDRA stardards are followed
5 secondary outcomes
Efficacy-Sensitivity Recovery Using ASIA Scale
Time frame: sensitivity before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
Time frame: Changes in the level of Chronic pain before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Efficacy- Changes in the Neurophysiological Parameters Measured as the Number of Patients With SSEPs (Somatosensory Evoked Potentials)
Time frame: Changes in the level neurophysiological parameters improvement (baseline visit) and 6, 12 months after surgery (follow-up period)
Efficacy-Urodynamic Studies in Terms of máximum Cystometric Capacity
Time frame: Urodynamic studies before surgery and 12 months after surgery (follow-up period)
Efficacy-modification of Magnetic Resonance Imaging (MRI)
Time frame: changes in the spinal cord morphology on neuroimaging studies before surgery and 12 months after surgery (follow-up period)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19364066Geffner LF, Santacruz P, Izurieta M, Flor L, Maldonado B, Auad AH, Montenegro X, Gonzalez R, Silva F. Administration of autologous bone marrow stem cells into spinal cord injury patients via multiple routes is safe and improves their quality of life: comprehensive case studies. Cell Transplant. 2008;17(12):1277-93. doi: 10.3727/096368908787648074.
- Individual participant dataSharing planned: Yes. nonymized individual data of participants will be shared with Authorities at the end of the Clinical Development Plan by the CTD (Common Technical Document). Results will be published in a scientific publication.
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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.
Jesus JV Vaquero Crespo, Dr. principal investigator
Hospital Universitario Puerta de Hierro Majadahonda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Mesenchymal stromal cell therapy in people with Spinal Cord Injury, run by Puerta de Hierro University Hospital at 1 site in Spain.
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 6 inclusion and 10 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 29 Mar 2019. 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 Spain. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety-Number of Adverse Events (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01909154, which also lists 1 linked publication.
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 29 Mar 2019.