Trial Outcomes & Findings for Safety Study of Local Administration of Autologous Bone Marrow Stromal Cells in Chronic Paraplegia (NCT NCT01909154)
NCT ID: NCT01909154
Last Updated: 2019-03-29
Results Overview
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
COMPLETED
PHASE1
12 participants
Up to 12 months
2019-03-29
Participant Flow
Participant milestones
| Measure |
Mesenchymal Stromal Cell Therapy
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 100x10\^6 followed by subarachnoid administration of 30x10\^6 MSCs,3 months later
Mesenchymal stromal cell therapy
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety Study of Local Administration of Autologous Bone Marrow Stromal Cells in Chronic Paraplegia
Baseline characteristics by cohort
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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 100x10\^6 followed by subarachnoid administration of 30x10\^6 MSCs,3 months later
Mesenchymal stromal cell therapy
|
|---|---|
|
Age, Continuous
|
40.5 years
STANDARD_DEVIATION 8.75 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
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12 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: 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
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
Outcome measures
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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
Mesenchymal stromal cell therapy
|
|---|---|
|
Safety-Number of Adverse Events
|
69 Adverse events
|
SECONDARY outcome
Timeframe: sensitivity before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)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.
Outcome measures
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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
Mesenchymal stromal cell therapy
|
|---|---|
|
Efficacy-Sensitivity Recovery Using ASIA Scale
6 months after surgery
|
189.83 units on a scale
Standard Deviation 27.83
|
|
Efficacy-Sensitivity Recovery Using ASIA Scale
9 months after surgery
|
200.75 units on a scale
Standard Deviation 34.40
|
|
Efficacy-Sensitivity Recovery Using ASIA Scale
12 months after surgery
|
213.25 units on a scale
Standard Deviation 37.19
|
|
Efficacy-Sensitivity Recovery Using ASIA Scale
Before Surgery
|
165.92 units on a scale
Standard Deviation 22.83
|
|
Efficacy-Sensitivity Recovery Using ASIA Scale
3 months after surgery
|
181.25 units on a scale
Standard Deviation 22.90
|
SECONDARY outcome
Timeframe: Changes in the level of Chronic pain before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)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.
Outcome measures
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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
Mesenchymal stromal cell therapy
|
|---|---|
|
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
9 months after surgery
|
2.42 units on a scale
Standard Deviation 0.90
|
|
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
12 months after surgery
|
2.58 units on a scale
Standard Deviation 0.79
|
|
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
Before Surgery
|
2.00 units on a scale
Standard Deviation 0.95
|
|
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
3 months after surgery
|
2.25 units on a scale
Standard Deviation 0.97
|
|
Efficacy-Changes in the Level of Chronic Pain Based on the IANR-SCIFRS Scale (Pain Section)
6 months after surgery
|
2.42 units on a scale
Standard Deviation 0.90
|
SECONDARY outcome
Timeframe: Changes in the level neurophysiological parameters improvement (baseline visit) and 6, 12 months after surgery (follow-up period)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.
Outcome measures
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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
Mesenchymal stromal cell therapy
|
|---|---|
|
Efficacy- Changes in the Neurophysiological Parameters Measured as the Number of Patients With SSEPs (Somatosensory Evoked Potentials)
6 months after surgery
|
5 number of patients with SSEPs
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|
Efficacy- Changes in the Neurophysiological Parameters Measured as the Number of Patients With SSEPs (Somatosensory Evoked Potentials)
Before Surgery
|
0 number of patients with SSEPs
|
|
Efficacy- Changes in the Neurophysiological Parameters Measured as the Number of Patients With SSEPs (Somatosensory Evoked Potentials)
12 months after surgery
|
7 number of patients with SSEPs
|
SECONDARY outcome
Timeframe: Urodynamic studies before surgery and 12 months after surgery (follow-up period)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.
Outcome measures
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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
Mesenchymal stromal cell therapy
|
|---|---|
|
Efficacy-Urodynamic Studies in Terms of máximum Cystometric Capacity
12 months after surgery
|
54.58 cm/H2O
Standard Deviation 22.88
|
|
Efficacy-Urodynamic Studies in Terms of máximum Cystometric Capacity
Before Surgery
|
77.50 cm/H2O
Standard Deviation 34.61
|
SECONDARY outcome
Timeframe: changes in the spinal cord morphology on neuroimaging studies before surgery and 12 months after surgery (follow-up period)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.
Outcome measures
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 Participants
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
Mesenchymal stromal cell therapy
|
|---|---|
|
Efficacy-modification of Magnetic Resonance Imaging (MRI)
Before Surgery
|
0 Patients
|
|
Efficacy-modification of Magnetic Resonance Imaging (MRI)
12 months after surgery
|
7 Patients
|
Adverse Events
Mesenchymal Stromal Cell Therapy
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Mesenchymal Stromal Cell Therapy
n=12 participants at risk
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 100x10\^6 followed by subarachnoid administration of 30x10\^6 MSCs,3 months later
Mesenchymal stromal cell therapy
|
|---|---|
|
Metabolism and nutrition disorders
High level of cholesterol in blood
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
General disorders
Pain
|
33.3%
4/12 • Number of events 4 • Along the study
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
4/12 • Number of events 5 • Along the study
|
|
Metabolism and nutrition disorders
High level of alkaline phosphatase in blood
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Infections and infestations
Perineal abscess
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Infections and infestations
Urinary tract infection
|
100.0%
12/12 • Number of events 24 • Along the study
|
|
Infections and infestations
Infectious mononucleosis
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
2/12 • Number of events 2 • Along the study
|
|
Injury, poisoning and procedural complications
Subcutaneous seroma
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Surgical and medical procedures
Hemorrhoidectomy
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Skin and subcutaneous tissue disorders
Pressure ulcer
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Blood and lymphatic system disorders
Iron deficiency anemia
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Nervous system disorders
Headache
|
16.7%
2/12 • Number of events 2 • Along the study
|
|
Nervous system disorders
Intercostal nerualgia
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Gastrointestinal disorders
Diarrhea
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Gastrointestinal disorders
Nausea
|
16.7%
2/12 • Number of events 2 • Along the study
|
|
General disorders
Saline extravasation
|
8.3%
1/12 • Number of events 2 • Along the study
|
|
General disorders
Local edema
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
General disorders
Hyperthermia
|
25.0%
3/12 • Number of events 5 • Along the study
|
|
Musculoskeletal and connective tissue disorders
Thoracic pain
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Musculoskeletal and connective tissue disorders
Muscle contracture
|
16.7%
2/12 • Number of events 2 • Along the study
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
25.0%
3/12 • Number of events 3 • Along the study
|
|
Psychiatric disorders
Anxiety
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Renal and urinary disorders
Urinary disconfort
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Vascular disorders
Hypertension
|
8.3%
1/12 • Number of events 1 • Along the study
|
|
Vascular disorders
Hypotension
|
8.3%
1/12 • Number of events 2 • Along the study
|
|
Vascular disorders
Orthostatic hypotension
|
8.3%
1/12 • Number of events 1 • Along the study
|
Additional Information
Dr. Vaquero Crespo
Hospital Universitario Puerta de Hierro Majadahonda, Madrid
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place