Efficacy Assessment of the Cell Therapy Medicine NC1 in Patients With Post-traumatic Syringomyelia (CME-LEM4)

• Sponsor: Puerta de Hierro University Hospital
• Information provided by (Responsible Party): Jesús Vaquero Crespo, M.D., Puerta de Hierro University Hospital

Study Description

Brief Summary:

The objective of the study is to determine if the cell therapy NC1 administered in the spinal cord is effective for the treatment of a post-traumatic syringomyelia. The post-traumatic syringomyelia is the development and progression of cyst filled with cerebrospinal fluid (CSF) within the spinal cord. The cell therapy NC1 consist on cells obtained from the bone marrow of the patient, that are cultured in vitro and administered in the spinal cord of the same patient.

Condition or disease	Intervention/treatment	Phase
Post-Traumatic Syringomyelia	Biological: NC 1 cell therapy	Phase 2

Detailed Description:

Phase II, Open, prospective, not controlled, not randomized clinical trial in patients affected by post-traumatic syringomyelia. The trial evaluates the efficacy of the cell therapy NC1 administered via intrathecal in the location of the injury. After the administration of the cell therapy, patients will undergo physiotherapy during the follow-up period (6 months). Patients will be evaluated at month 3 and month 6 after the NC1 administration.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Efficacy Assessment of the Cell Therapy Medicine NC1 in Patients With Post-traumatic Syringomyelia
Study Start Date :	March 2016
Actual Primary Completion Date :	February 7, 2018
Actual Study Completion Date :	February 7, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: NC 1 cell therapy; All patients will be treated with the same treatment: NC1 cell therapy	Biological: NC 1 cell therapy; All patients will be treated with NC1

Outcome Measures

Primary Outcome Measures :

1. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia using the ASIA scale (American Spinal Injury Association [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using ASIA scale (American Spinal Injury Association)

Secondary Outcome Measures :

1. Safety, by the assessment of the adverse events of the study [ Time Frame: 1 year ]
   Adverse events
2. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia assessed with the IANR-SCIFRS scale (Injury Functional Rating Scale) [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using IANR-SCIFRS scale (Injury Functional Rating Scale)
3. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia in terms of spams frequency [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using PENN scale (spams frequency score)
4. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia in term of spasticity [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using Ashworth scale (spasticity)
5. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia using the Visual Analog Scale [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using EVA scale (Visual Analog Scale)
6. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia in terms of bladder functionality [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using GEFFNER scale (bladder functionality)
7. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia using the Behavior Dimensions Scale [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Neurological evaluation is done using BDS scales (Behavior Dimensions Scale)
8. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia in terms of somatosensory or motor evoked potentials [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   Present of somatosensory or motor evoked potentials
9. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia by electromyography [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
   EMG (Electromyography)
10. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia studying the spinal cord morphology [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
    Spinal cord morphology (by Magnetic Resonance)
11. Efficacy of the treatment with NC1 in terms of improvement of neurological sequelae in patients with post traumatic syringomyelia in terms of defecatory function [ Time Frame: Pretreatment, month 3 post treatment, month 6 post treatment ]
    Neurological evaluation is done assessing the defecatory function

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 70 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Patients with traumatic medullar injury (levels A, B, C or D of the ASIA scale) and associated syringomyelia in at least three spinal segments, and with neurological deficit clinically stable at least 6 months prior to treatment.
• Previous studies in Neurophysiology, MR, Urology (if data on neurogenic bowel exists), defecatory function (if data on neurogenic intestine exists)
• Age between 18 and 70 years old.
• Presence of syringomyelia based on a neuro-image (MR)
• Patients will compromise to use anticonceptive measures from the cell extraction until 6 months after the administration of the treatment.
• Patients will compromise to a clinical follow-up and to perform physical therapy, one hour daily five days per week during the treatment period.
• Patients should sign an written informed consent.
• Haematological and creatinin parameters, SGOT and SGPT into the normal ranges.

Exclusion Criteria:

• Patients under 18 or above 70 years old
• Pregnancy or breastfeeding
• Neoplasia in the last 5 years
• Patients with systemic diseases that increase the risk of the surgical intervention
• Genetics alterations that could conduct to cellular transformation during the cellular expansion phase.
• Patients not really sure of their cooperation to follow the physical therapy or clinical controls during the study.
• Additional neurodegenerative diseases
• Drug consuming, psychiatric disease or allergy to proteins used during cellular expansion
• HIV or syphilis positive serologies
• Active Hepatitis B or c, based on serologies
• Any other reasons according to the investigator criteria.

Contacts and Locations

Sponsors and Collaborators

Puerta de Hierro University Hospital

Investigators

Layout table for investigator information

Principal Investigator:	Jesús Vaquero Crespo, M.D.	Hospital Universitario Puerta de Hierro-Majadahonda

More Information

Publications:

Vaquero J, Zurita M. Bone marrow stromal cells for spinal cord repair: a challenge for contemporary neurobiology. Histol Histopathol. 2009 Jan;24(1):107-16. doi: 10.14670/HH-24.107. Review.

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.

Otero L, Zurita M, Bonilla C, Aguayo C, Rico MA, Rodríguez A, Vaquero J. Allogeneic bone marrow stromal cell transplantation after cerebral hemorrhage achieves cell transdifferentiation and modulates endogenous neurogenesis. Cytotherapy. 2012 Jan;14(1):34-44. doi: 10.3109/14653249.2011.608349. Epub 2011 Sep 23.

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.

Huang H, Xi H, Chen L, Zhang F, Liu Y. Long-term outcome of olfactory ensheathing cell therapy for patients with complete chronic spinal cord injury. Cell Transplant. 2012;21 Suppl 1:S23-31. doi: 10.3727/096368912X633734.

Layout table for additonal information

Responsible Party:	Jesús Vaquero Crespo, M.D., M.D., Puerta de Hierro University Hospital
ClinicalTrials.gov Identifier:	NCT02807142 History of Changes
Other Study ID Numbers:	CME-LEM4
First Posted:	June 21, 2016
Last Update Posted:	April 5, 2018
Last Verified:	April 2018
Individual Participant Data (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.

Additional relevant MeSH terms:

Layout table for MeSH terms

Syringomyelia; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases