Administration of Expanded Autologous Adult Bone Marrow Mesenchymal Cells in Established Chronic Spinal Cord Injuries

• ClinicalTrials.gov Identifier: NCT02570932
• Recruitment Status: Completed
• First Posted: October 7, 2015
• Last Update Posted: April 5, 2018
• Sponsor: Puerta de Hierro University Hospital
• Information provided by (Responsible Party): Jesús Vaquero Crespo, M.D., Puerta de Hierro University Hospital

Tracking Information

• First Submitted Date: October 2, 2015
• First Posted Date: October 7, 2015
• Last Update Posted Date: April 5, 2018
• Study Start Date: July 2015
• Actual Primary Completion Date: December 4, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 5, 2016)

Changes in IANR-SCIFRS score are considerate for the motor and sensory functions evaluation. [ Time Frame: from baseline until the end of the follow up period (24 months) ]

Efficacy evaluation by measuring the change in motor and sensory functions by using the international Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS). This scale includes 9 categories with 16 items in total (plus one optional category). The maximum possible score is 48; the lowest possible score is 0.

Original Primary Outcome Measures (submitted: October 5, 2015)

Change in motor and sensory functions [ Time Frame: from baseline until the end of the follow up period (24 months) ]

Change in the following scale are considerate for the efficacy evaluation: the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), the Penn Spasm Frequency Scale that is Composed of 2-parts: the first is a self-report measure with items on 5-point scales developed to augment clinical ratings of spasticity and provides a more comprehensive assessment of spasticity, the visual analogue scale EVA, the Blepharospasm Disability Scale (BDS) and the GEFFNER scale. multiple measurements data will be collected at the end of the trial and aggregated to arrive at one reported value that will obtained by Multiple linear regression and factorial analysis.

Current Secondary Outcome Measures (submitted: August 25, 2017)

• Neurotrophic factors levels in Cerebrospinal fluid (CSF) and/ or Number of Adverse Events related to treatment [ Time Frame: from baseline to 24 months ]
  The clinical evaluation of possible adverse effects is performed throughout the entire study duration and will be measured by descriptive analysis
• Changes in PENN score are considerate for the motor and sensory functions evaluation [ Time Frame: from baseline until the end of the follow up period (24 months) ]
  Efficacy evaluation by measuring the change in motor and sensory functions by using the Penn Spasm Frequency Scale that is Composed of 2-parts: the first is a self-report measure with items on 5-point scales developed to augment clinical ratings of spasticity and provides a more comprehensive assessment of spasticity
• Changes in VAS score are considerate for quantification of pain [ Time Frame: from baseline until the end of the follow up period (24 months) ]
  Efficacy evaluation by measuring the change in pain by using the visual analogue scale (VAS). The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks, depending on his feel of pain.
• Changes in BDS score are considerate for the Assessment of the functional status [ Time Frame: from baseline until the end of the follow up period (24 months) ]
  Efficacy evaluation by measuring the change in the Blepharospasm Disability Scale (BDS)
• Changes in GEFFNER score are considerate for the Assessment of the functional status [ Time Frame: from baseline until the end of the follow up period (24 months) ]
  Efficacy evaluation by measuring the change in the GEFFNER score

Original Secondary Outcome Measures (submitted: October 5, 2015)

Neurotrophic factors levels in Cerebrospinal fluid (CSF) and/ or Number of Adverse Events related to treatment [ Time Frame: from baseline to 24 months ]

The clinical evaluation of possible adverse effects is performed throughout the entire study duration and will be measured by descriptive analysis

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Administration of Expanded Autologous Adult Bone Marrow Mesenchymal Cells in Established Chronic Spinal Cord Injuries
• Official Title: Intrathecal Administration (Pattern 100/3) of Expanded Autologous Adult Bone Marrow Mesenchymal Stem Cells in Established Chronic Spinal Cord Injuries
• Brief Summary: The purpose of this study is to analyze the potential clinical efficacy of intrathecal administration, in the subarachnoid space, of in vitro expanded autologous adult bone marrow mesenchymal stem cells in the treatment of patients with established chronic spinal cord injury (LEM).

Detailed Description

This is a clinical trial phase II, single-center, non-randomized, uncontrolled, open prospective follow-up of a cohort of patients with chronic spinal cord injury.

Patients are treated with repeated administrations of in vitro expanded autologous adult bone marrow mesenchymal stem cells.

The expanded cells are administered in the subarachnoid space by lumbar puncture. The minimum duration of the follow-up period for each patient is 10 months after the first administration.

The study duration is 24 months, that include recruiting, treatment and follow period for all patients. For each patient at the first day will be administered the first cellular doses, then 3 doses will be administrated every 3 months. At the end of the clinical trial, a completed check of all obtained parameters will be performed.

It is considered Day 1 for each patient the first day of the first cell administration. The remaining 2 doses will be administered at intervals of 3 months from the first administration (of the treatment period after, months 4 and 7). At the end of the study will be performed a full assessment of the variables collected along the study trial.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Spinal Cord Injury

Intervention

Biological: Autologous Mesenchymal Bone Marrow Cell

Suspension in autologous plasma cell of Adult mesenchymal stem cells expanded autologous bone marrow.

Route of administration: Intrathecal in subarachnoid space by lumbar puncture.Total dose of 300 x 106 CME, divided in 3 injections of 100 x 106 CME, with intervals of three months between each administration

Study Arms

Experimental: Autologous Mesenchymal Bone Marrow Cell

All patients will be treated with the same treatment: Adult Autologous Mesenchymal Bone Marrow expanded Stem Cell (CME)

Pharmaceutical form: Suspension in autologous plasma cell Route of administration: Intrathecal in subarachnoid space by lumbar puncture. Dose: Total dose of 300 x 106 CME, given in 3 injections of 100 x 106 CME, at intervals of 3 months between each administration.

Intervention: Biological: Autologous Mesenchymal Bone Marrow Cell

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 5, 2015): 10
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 4, 2017
• Actual Primary Completion Date: December 4, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Spinal cord injury (Level A, B, C or D in ASIA scales), clinically stable for at least 6 months prior to study start.
2. Previous studies of Neurophysiology, MRI and Urology to allow useful baseline, in order that they can be compared with the same scans following treatment, and to obtain objective data of potential efficacy.
3. Age between 18 and 70 years.
4. Men and women of childbearing age must compromise to use contraceptives from the time at which the removal of cells from the bone marrow is performed until 6 months after the Mesenchymal Stem Cells (MSC) last administration by lumbar puncture.
5. Possibility of follow up and ability to perform ambulatory physical therapy throughout all treatment period.
6. Written informed consent, according to the law in force.
7. Hematologic, creatinine, Serum glutamic oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT) parameters, within the normal range, according to laboratory standards. However, slight modifications that are considered significant in the context of treatment to be performed, according to the criterion of the research team, are accepted.

Exclusion Criteria:

1. Age below 18 years or above 70.
2. Pregnancy or lactation.
3. Current neoplastic disease or in the previous 5 years (diagnosed or treated).
4. Patients with systemic disease that represents an added risk to treatment.
5. Alterations in the genetic study performed to discard risk cell transformation in the expansion process.
6. Patients with doubts about possible cooperation in the maintenance physical therapy or in the controls carried out during the study
7. Neurodegenerative disease added.
8. History of substance abuse, psychiatric disease or allergy to protein products used in the process of cell expansion.
9. Positive serology for HIV and syphilis.
10. Active Hepatitis B or Hepatitis C, according to serology analysis.
11. If in the opinion of the researcher there is some other reason why the patient is not considered candidate for the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT02570932
• Other Study ID Numbers: CME-LEM3; 2014-005613-24 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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
• Time Frame: Starting at CTD submission to authorities.
• Access Criteria: Spanish competent authority.

• Current Responsible Party: Jesús Vaquero Crespo, M.D., Puerta de Hierro University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Puerta de Hierro University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jesús JV Vaquero Crespo, MD.; Hospital Universitario Puerta de Hierro-Majadahonda

• PRS Account: Puerta de Hierro University Hospital
• Verification Date: April 2018