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Subarachnoid Administrations of Adults Autologous Mesenchymal Stromal Cells in SCI

Primary Purpose

Spinal Cord Injury

Status

Completed

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

Adult Autologous Mesenchymal Bone Marrow Cell

About this trial

This is an interventional treatment trial for Spinal Cord Injury focused on measuring Analyze clinical efficacy of subarachnoid administration of, autologous BMSC expanded "in vitro"

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Incomplete SCI
Neurological deficit clinically stable at least 12 months prior to treatment, and with a minimum of one-year evolution after SCI.
Neurophysiological confirmation of incomplete SCI.
The MRI study that morphologically evaluate the SCI.
Age between 18 and 70 years
Thread Men and women will compromise to use anticonceptive issues from first cell´s extraction to 6 months after last cell´s administration.
Ability to attend clinical follow-up and perform physical therapy through the treatment period.
Written and signed informed consent, according to the local regulation.
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:

A classification in ASIA and FRANKEL clinical scales to evaluate the SCI.
Neurophysiological records that confirm the complete SCI.
Age below 18 years or above 70.
Pregnancy or lactation.
Malignancy disease diagnosed or treated within the last 5 years.
Patients with systemic disease that represents and additional risk to treatment.
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.
Inability to assess the SCI features through MRI either noise due to spinal stabilization systems or any other cause.
Patients currently under hematopoietic growth factors treatment or who required or maintained anticoagulation.
Neurodegenerative disease additional.
History of substance abuse, psychiatric disease or allergy to the protein products used in the process of cell expansion.
Positive serology for HIV and syphilis.
Active Hepatitis B or Hepatitis C.
With other reason that would consider the patient ineligible for cell therapy according to the investigators judgment.

Sites / Locations

Hospital Puerta de Hierro

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous Mesenchymal Bone Marrow Cell

Arm Description

All patients will be treated with the same treatment: Adult Autologous Mesenchymal Bone Marrow Cell

Outcomes

Primary Outcome Measures

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.

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.

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.

Efficacy-IANC-SCIFRS Scale

-Changes in IANC-SCIFRS scale Ranges score: 0 to 48. Being 0 severe degree of disability and 48 normal value.

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.

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

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.

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

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.

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-Urodynammic in Terms of Detrusor Pressure

Urodynamic studies in terms of detrusor pressure (decrease on detrusor pressure is considered a clinical improvement)

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.

Efficacy-Urodynamic Studies Maximum Cystometric Capacity

Urodynamic studies in terms of Maximum cystometric capacity

Efficacy-modification of Magnetic Resonance Imaging (MRI)

Number of patients with changes in morphology of injury compared with basal images

Secondary Outcome Measures

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).

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.

Full Information

NCT ID

NCT02165904

First Posted

May 6, 2014

Last Updated

May 14, 2019

Sponsor

Puerta de Hierro University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02165904

Brief Title

Subarachnoid Administrations of Adults Autologous Mesenchymal Stromal Cells in SCI

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2019

Overall Recruitment Status

Completed

Study Start Date

May 2014 (undefined)

Primary Completion Date

May 2016 (Actual)

Study Completion Date

May 2016 (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

5. Study Description

Brief 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.

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) .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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Cord Injury

Keywords

Analyze clinical efficacy of subarachnoid administration of, autologous BMSC expanded "in vitro"

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Autologous Mesenchymal Bone Marrow Cell

Arm Type

Experimental

Arm Description

All patients will be treated with the same treatment: Adult Autologous Mesenchymal Bone Marrow Cell

Intervention Type

Biological

Intervention Name(s)

Adult Autologous Mesenchymal Bone Marrow Cell

Intervention Description

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

Primary Outcome Measure Information:

Title

Efficacy-Sensivity Improvement Using the ASIA Score

Description

Time Frame

measure before treatment (baseline visit), 3, 6, 9 and 12 months after surgery

Title

Efficacy- Changes in Functional Independence Measure Scale

Description

Time Frame

measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery

Title

Efficacy-Change in Barthel Score

Description

- 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.

Time Frame

measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery

Title

Efficacy-IANC-SCIFRS Scale

Description

-Changes in IANC-SCIFRS scale Ranges score: 0 to 48. Being 0 severe degree of disability and 48 normal value.

Time Frame

Changes in IANC-SCIFRS scale before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)

Title

Efficacy-Changes in PENN Score.

Description

- 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.

Time Frame

measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery

Title

Changes in ASHWORTH Score

Description

Time Frame

measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery

Title

Efficacy-Changes in EVA Score

Description

• 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.

Time Frame

measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery

Title

Efficacy- Changes in Geffner Score

Description

Time Frame

Changes in Geffner scale before surgery (baseline visit) and 3, 6, 9, 12 months after surgery (follow-up period)

Title

Efficacy- Changes in NBD Score

Description

Time Frame

measure before treatment (baseline visit), 3, 6,9 and 12 months after surgery

Title

Efficacy-Changes in the Neurophysiological Parameters (SSEPs, Somatosensory Evoked Potentials)

Description

Changes in the neurophysiological parameters (SSEPs, somatosensory evoked potentials) measured as the number of patients that improved along the study.

Time Frame

Efficacy-measure before treatment (baseline visit), 6, and 12 months after surgery

Title

Efficacy-Urodynammic in Terms of Detrusor Pressure

Description

Urodynamic studies in terms of detrusor pressure (decrease on detrusor pressure is considered a clinical improvement)

Time Frame

Urodynamic studies before surgery, and at 6 and 12 months after surgery (follow-up

Title

Efficacy-Urodynamic Studies Bladder Compliance

Description

Time Frame

measure before treatment (baseline visit), 6 and 12 months after surgery

Title

Efficacy-Urodynamic Studies Maximum Cystometric Capacity

Description

Urodynamic studies in terms of Maximum cystometric capacity

Time Frame

Urodynamic studies before surgery, and at 6 and 12 months after surgery (follow-up

Title

Efficacy-modification of Magnetic Resonance Imaging (MRI)

Description

Number of patients with changes in morphology of injury compared with basal images

Time Frame

before (baseline visit) and at 12 months

Secondary Outcome Measure Information:

Title

Number of Adverse Events .

Description

- 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).

Time Frame

Up to 12 months

Title

Efficacy- Expression of Neurotrophins in CSF (CerebroSpinal Fluid) Samples

Description

Time Frame

Basal and 10 months after the administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Incomplete SCI Neurological deficit clinically stable at least 12 months prior to treatment, and with a minimum of one-year evolution after SCI. Neurophysiological confirmation of incomplete SCI. The MRI study that morphologically evaluate the SCI. Age between 18 and 70 years Thread Men and women will compromise to use anticonceptive issues from first cell´s extraction to 6 months after last cell´s administration. Ability to attend clinical follow-up and perform physical therapy through the treatment period. Written and signed informed consent, according to the local regulation. 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: A classification in ASIA and FRANKEL clinical scales to evaluate the SCI. Neurophysiological records that confirm the complete SCI. Age below 18 years or above 70. Pregnancy or lactation. Malignancy disease diagnosed or treated within the last 5 years. Patients with systemic disease that represents and additional risk to treatment. 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. Inability to assess the SCI features through MRI either noise due to spinal stabilization systems or any other cause. Patients currently under hematopoietic growth factors treatment or who required or maintained anticoagulation. Neurodegenerative disease additional. History of substance abuse, psychiatric disease or allergy to the protein products used in the process of cell expansion. Positive serology for HIV and syphilis. Active Hepatitis B or Hepatitis C. With other reason that would consider the patient ineligible for cell therapy according to the investigators judgment.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jesús JV Vaquero Crespo, M.D.

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

Anonymized 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

21163325

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.

Results Reference

background

PubMed Identifier

21208021

Citation

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.

Results Reference

background

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Subarachnoid Administrations of Adults Autologous Mesenchymal Stromal Cells in SCI

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