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Safety Study of Local Administration of Autologous Bone Marrow Stromal Cells in Chronic Paraplegia (CME-LEM1)

Primary Purpose

Spinal Cord Injury

Status
Completed
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
Mesenchymal stromal cell therapy
Sponsored by
Puerta de Hierro University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Cord Injury focused on measuring neurophysiological parameters improvement, spinal cord injury, biology therapy

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion criteria:

  • 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
  • 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.

Sites / Locations

  • Hospital Puerta de Hierro

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mesenchymal stromal cell therapy

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
July 7, 2013
Last Updated
March 28, 2019
Sponsor
Puerta de Hierro University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01909154
Brief Title
Safety Study of Local Administration of Autologous Bone Marrow Stromal Cells in Chronic Paraplegia
Acronym
CME-LEM1
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
March 2013 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Puerta de Hierro University Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Cord Injury
Keywords
neurophysiological parameters improvement, spinal cord injury, biology therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mesenchymal stromal cell therapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Biological
Intervention Name(s)
Mesenchymal stromal cell therapy
Other Intervention Name(s)
BMMSCs= Bone Marrow Mesenchymal Stem Cells
Intervention Description
Stem cells administration locally
Primary Outcome Measure Information:
Title
Safety-Number of Adverse Events
Description
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
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Efficacy-Sensitivity Recovery Using ASIA Scale
Description
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.
Time Frame
sensitivity before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Title
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
Description
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.
Time Frame
Changes in the level of Chronic pain before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Title
Efficacy- Changes in the Neurophysiological Parameters Measured as the Number of Patients With SSEPs (Somatosensory Evoked Potentials)
Description
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.
Time Frame
Changes in the level neurophysiological parameters improvement (baseline visit) and 6, 12 months after surgery (follow-up period)
Title
Efficacy-Urodynamic Studies in Terms of máximum Cystometric Capacity
Description
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.
Time Frame
Urodynamic studies before surgery and 12 months after surgery (follow-up period)
Title
Efficacy-modification of Magnetic Resonance Imaging (MRI)
Description
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.
Time Frame
changes in the spinal cord morphology on neuroimaging studies before surgery and 12 months after surgery (follow-up period)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion criteria: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jesus JV Vaquero Crespo, Dr.
Organizational Affiliation
Hospital Universitario Puerta de Hierro-Majadahonda
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
19364066
Citation
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.
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Safety Study of Local Administration of Autologous Bone Marrow Stromal Cells in Chronic Paraplegia

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