Subarachnoid Administrations of Adults Autologous Mesenchymal Stromal Cells in SCI

Spinal Cord Injury Clinical Trial

Official title:

Subarachnoid Administrations of Adults Autologous Mesenchymal Stromal Cells in Patients Suffering Incomplete Spinal Cord Injury (SCI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02165904
• Other study ID #: CME-LEM2
• Secondary ID: 2011-005684-24
• Status: Completed
• Phase: Phase 1
• Start date: May 2014
• Est. completion date: May 2016

Study information

• Verified date: May 2019
• Source: Puerta de Hierro University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study goes on 24 months, with recruiting, treatment and follow period for all patients. The first day for each patient will be the first cellular administration. 3 doses will be administrated every 3 months from first dose.

When the clinical trial finishes, it will be done a completed check of all obtained parameters.

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) .10 patients will be included with this injury.

Primary objective: Analyze the possible clinical efficacy of administration of main adult mesenchymal autologous cells expanded "in vitro" in patients with incomplete and chronically established SCI.

Secondary objectives: Confirm the safety of treatment, and study possible changes in the cerebrospinal fluid (CSF) levels (Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), Nerve Growth Factor 3 and 4(NT3 and NT4) after subarachnoid administration of BMMC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Incomplete SCI

2. Neurological deficit clinically stable at least 12 months prior to treatment, and with a minimum of one-year evolution after SCI.

3. Neurophysiological confirmation of incomplete SCI.

4. The MRI study that morphologically evaluate the SCI.

5. Age between 18 and 70 years

6. Thread Men and women will compromise to use anticonceptive issues from first cell´s extraction to 6 months after last cell´s administration.

7. Ability to attend clinical follow-up and perform physical therapy through the treatment period.

8. Written and signed informed consent, according to the local regulation.

9. Hematologic and creatinin parameters, SGOT and SGPT, within the normal range, according to laboratory standards considering that small variations could be accepted based on clinical study team criteria.

Exclusion Criteria:

1. A classification in ASIA and FRANKEL clinical scales to evaluate the SCI.

2. Neurophysiological records that confirm the complete SCI.

3. Age below 18 years or above 70.

4. Pregnancy or lactation.

5. Malignancy disease diagnosed or treated within the last 5 years.

6. Patients with systemic disease that represents and additional risk to treatment.

7. Patients with uncertain commitment to follow the physical therapy and clinical visits as well as patient with a negative input in the previous phycological assessment.

8. Inability to assess the SCI features through MRI either noise due to spinal stabilization systems or any other cause.

9. Patients currently under hematopoietic growth factors treatment or who required or maintained anticoagulation.

10. Neurodegenerative disease additional.

11. History of substance abuse, psychiatric disease or allergy to the protein products used in the process of cell expansion.

12. Positive serology for HIV and syphilis.

13. Active Hepatitis B or Hepatitis C.

14. With other reason that would consider the patient ineligible for cell therapy according to the investigators judgment.

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Biological:
• Adult Autologous Mesenchymal Bone Marrow Cell
Diagnosed patients with incomplete spinal cord injury and chronically established SCI will be treated with Adult Autologous Mesenchymal Bone Marrow Cells.

Locations

Country	Name	City	State
Spain	Hospital Puerta de Hierro	Majadahonda	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Puerta de Hierro University Hospital

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Otero L, Zurita M, Bonilla C, Aguayo C, Vela A, Rico MA, Vaquero J. Late transplantation of allogeneic bone marrow stromal cells improves neurologic deficits subsequent to intracerebral hemorrhage. Cytotherapy. 2011 May;13(5):562-71. doi: 10.3109/14653249.2010.544720. Epub 2011 Jan 5. — View Citation

Vaquero J, Zurita M. Functional recovery after severe CNS trauma: current perspectives for cell therapy with bone marrow stromal cells. Prog Neurobiol. 2011 Mar;93(3):341-9. doi: 10.1016/j.pneurobio.2010.12.002. Epub 2010 Dec 14. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy-Sensivity Improvement Using the ASIA Score	Sensitivity improvement 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 10 patients were obtained at all the time points and statistically analyzed.	measure before treatment (baseline visit), 3, 6, 9 and 12 months after surgery
Primary	Efficacy- Changes in Functional Independence Measure Scale	- Changes in Functional Independence Measure scale (NIF scale), score at the beginning, through and the end of the treatment.; Ranges score: 18 to 126. Being 18 total patient dependency and 126 total patient independence.	measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery
Primary	Efficacy-Change in Barthel Score	- Changes in Barthel score at the beginning, through and the end of the treatment.; Ranges score: 0 to 100. Being 0 total patient dependency and 100 total patient independence.	measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery
Primary	Efficacy-IANC-SCIFRS Scale	-Changes in IANC-SCIFRS scale; Ranges score: 0 to 48. Being 0 severe degree of disability and 48 normal value.	Changes in IANC-SCIFRS scale before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Primary	Efficacy-Changes in PENN Score.	- Changes in PENN score at the beginning, through and the end of the treatment; Ranges score: 0 to 4. Being 0 absence of spasms and 4 frequency greater than 10 spasms per hour.	measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery
Primary	Changes in ASHWORTH Score	- Changes in ASHWORTH score at the beginning, through and the end of the treatment; Ranges score: 0 to 4. Being 0 when there isn´t increase in muscle tone when stretching, and 4 when there is rigid affected follow-up in flexion or extension	measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery
Primary	Efficacy-Changes in EVA Score	• Changes in EVA score at the beginning, through and the end of the treatment; Ranges score: 0 to 10. Being 0 absence of pain and 10 the worst pain.	measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery
Primary	Efficacy- Changes in Geffner Score	changes in Geffner score before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period); Ranges score: 0 to 6. Being 0 absence of bladder control and 6 total control of bladder	Changes in Geffner scale before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)
Primary	Efficacy- Changes in NBD Score	changes in NBD score before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period); Ranges score: 0 to 47. 0-6 is very minor dysfunction. 7-9 is minor dysfunction. 10-13 is moderate dysfunction; and 14 or more is severe dysfunction.	measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery
Primary	Efficacy-Changes in the Neurophysiological Parameters (SSEPs, Somatosensory Evoked Potentials)	Changes in the neurophysiological parameters (SSEPs, somatosensory evoked potentials) measured as the number of patients that improved along the study.	Efficacy-measure before treatment (baseline visit), 6, and 12 months after surgery
Primary	Efficacy-Urodynammic in Terms of Detrusor Pressure	Urodynamic studies in terms of detrusor pressure (decrease on detrusor pressure is considered a clinical improvement)	Urodynamic studies before surgery, and at 6 and 12 months after surgery (follow-up
Primary	Efficacy-Urodynamic Studies Bladder Compliance	Urodynamic studies in terms of Bladder compliance. Bladder compliance is the result of a mathematical calculation of volume responsible for 1 cm H2O pressure rise measured during a cystometric filling; . It gives an indication on how the different mechanisms in the bladder wall react on stretching.; It is obvious that compliance figures can vary widely in groups which makes it difficult to define limits of normality.	measure before treatment (baseline visit), 6 and 12 months after surgery
Primary	Efficacy-Urodynamic Studies Maximum Cystometric Capacity	Urodynamic studies in terms of Maximum cystometric capacity	Urodynamic studies before surgery, and at 6 and 12 months after surgery (follow-up
Primary	Efficacy-modification of Magnetic Resonance Imaging (MRI)	Number of patients with changes in morphology of injury compared with basal images	before (baseline visit) and at 12 months
Secondary	Number of Adverse Events .	- The safety will be valued with number of adverse events related with administration of subarachnoid autologous Bone Marrow Expanded Mesenchymal Cells in Incomplete Spinal Cord Injury (SCI).	Up to 12 months
Secondary	Efficacy- Expression of Neurotrophins in CSF (CerebroSpinal Fluid) Samples	Changes in expression of neurotrophins in CSF (CerebroSpinal Fluid) samples obtained previously to first administration of cell therapy, and previously to the last administration, at month 10, in order to study the variability in the expression of neurotrophins along time. The mean+SD (standard deviation) at each time point was obtained. The tested neurotrophins were: BDNF.	Basal and 10 months after the administration