Clinical trial NCT03933072: Autologous Bulbar Olfactory Ensheathing Cells and Nerve Grafts for Treatment of Patients With Spinal Cord Transection
Official title: Evaluation of the Possibility of Induction of Functional Axon Regeneration in Patients With Complete Spinal Cord Injuries Using Autologous Bulbar Olfactory Ensheathing Cells and Techniques of Bridging of the Spinal Cord.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Spinal Cord Injury at C5-Th10 Level With Complete Lesion
Spinal Cord Transection
Keywords: complete spinal cord injury, spinal cord transection, olfactory ensheathing cells, olfactory fibroblasts, Glial Neuropatch, nerve grafts
Lead sponsor: Nicholls Spinal Injury Foundation
Sponsor class: OTHER
Collaborators: name: Wroclaw Medical University
name: Akson, Neuro-Rehabilitation Center for the Treatment of Spinal Cord Injuries
name: University College, London
name: Poznan University of Medical Sciences
First posted: 2019-05-01
Enrollment: 2
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: interventional study, parallel assessment, open label, non-randomized, safety-efficacy study; sponsored clinical trial;
Primary purpose: TREATMENT

Brief summary: The purpose of this experimental therapy is to evaluate the safety and efficacy of transplantation of autologous olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts (ONFs) obtained from the olfactory bulb with simultaneous reconstruction of the posttraumatic spinal cord gap with peripheral nerve grafts, in patients with chronic complete spinal cord injury. The treatment will be performed in two patients that have sustained an anatomically complete spinal cord transection between the spinal cord segments C5 and Th10.

All patients wanting to participate in this study have to send their application at the address:

walk-again-project.org

Detailed description: The "Wrocław Walk Again" project is a continuation of the innovative experimental therapy involving reconstruction of patient's severed spinal cords, using their own olfactory glial cells from the olfactory bulb as well as implants from peripheral nerves. The first operation of its kind was performed in 2012. The reconstruction of the cord was a success: the patient regained partial feeling and volitional mobility in paralysed limbs (Cell Transplantation, Vol. 23, pp. 1631-1655, 2014). The experiment's success provided inspiration to continue with the project in order to assess the safety and effectiveness of the therapy applied. The continuation involves planning to qualify two patients with traumatic spinal cord injury, who will then be given treatment and physiotherapy. The programme will be conducted in Wroclaw, Poland, by an interdisciplinary team of doctors and scientists. The Nicholls Spinal Injury Foundation (UK) will be making a significant contribution to the project. Due to this, participants will not need to pay for their experimental treatment or physiotherapy.

The main goal of the study is to answer the question if there is possible to evoke functional regeneration of severed spinal cord axons after a two-stage surgical intervention in patients sustaining a complete spinal cord transection between the spinal cord segments C5 and Th10. Patients with clinically, electrophysiologically and radiologically features of complete spinal cord injury will undergo an 8-month neurorehabilitation regimen. Patients who will not show electrophysiological and clinical signs of recovery from the spinal cord injury will enter the surgical part of the study.

During the first surgery the patient's own olfactory bulb will be obtained. The human autologous olfactory ensheathing glia and olfactory fibroblast isolated from the olfactory bulb will be used for production of Glial Neuropatch in accordance with the methodology adjusted in grant number GR-797/NCN/2013 and 2012/06/M/NZ4/00138, in a laboratory facility, in accordance with the good manufacture procedures (GMP). The final Product will consist of the aforementioned cell suspension embedded with collagen scaffold. The European Medicines Agency/Committee for Advanced Therapies (EMA/CAT) considers that the Product Glial Neuropatch falls within the definition of a tissue engineered product of an advanced therapy medicinal product (decision EMA/CAT/293903/2018 from 22 June 2018: Scientific recommendation on classification of advanced therapy medicinal products Article 17 - Regulation (EC) No 1394/2007).

The second surgery will consist of laminectomy/laminotomy, midline durotomy above the area of spinal cord lesion, detethering of the spinal cord from fibrous adhesions, resection of the posttraumatic spinal cord glial scar, delivering of cultured OEC/ONFs explants (Glial Neuropatch) to the area of spinal cord injury and finally bridging of the spinal cord gap by harvested autologous sural nerve grafts.

After discharge from the hospital, the patients will be subjected to a minimum 2-year neurorehabilitation in accordance with the same program as before the operation.

Eligibility criteria: Inclusion Criteria:

1. A single spinal cord injury between vertebral levels C5-Th10 with a total anatomic disruption of continuity.
2. Myelopathy not exceeding 2 spinal cord segments as confirmed by MRI.
3. Complete loss of sensory and motor function below the injury, confirmed in serial control clinical studies (ASIA Category A) and neurophysiological studies (MEP, SSR, EPT, EMG, ENG, von Frey's filaments)
4. Age from 16 to 65 years.
5. Patient undergoing continuous rehabilitation.
6. Good patient motivation and cooperation, no mental disturbances.
7. Patient is ready to stay with an accompanying person for at least 3 years in Poland.
8. Patient without cardiac disease and without epilepsy, does not have peacemaker or any electronic or ferromagnetic implants.

Exclusion Criteria:

1. A coexisting lesion of the nervous system.
2. Progressive post-traumatic syringomyelia.
3. Significant spinal stenosis or instability.
4. Muscle atrophy or joint ossifications.
5. Severe systemic disease such as neoplasm, contagious disease, diabetes etc.
6. Chronic sinusitis destroying the paranasal sinuses, tumors of nasal cavities or patients with hyposmia in repetitive smell perception tests will be excluded.
7. Implants or the health status described in point 8 (see above).

Note: All patients wanting to participate in this study have to send their application via the walk-again-project.org recruitment website!

Primary outcomes:
measure: improvement of the neurologic state measured by the American Spinal Injury Association (ASIA) score.
timeFrame: up to 2 years postoperatively
measure: improvement of the strenght of trunk muscles measured by the Berg Balance scale
timeFrame: up to 2 years postoperatively
measure: improvement of neurologic state measured with tests of deep sensation
timeFrame: up to 2 years postoperatively
measure: improvement of neurologic state measured with tests of vibration
timeFrame: up to 2 years postoperatively
measure: improvement of neurologic state measured with tests of joint position sense
timeFrame: up to 2 years postoperatively
Secondary outcomes:
measure: decrease of muscle spasticity for at least 1 level measured the Ashworth scale
timeFrame: tested monthly for at least 2 years postoperatively
measure: Spinal Cord Assessment Tool for Spastic Reflexes ( SCATS)
timeFrame: tested monthly for at least 2 years postoperatively
measure: improvement of locomotion ability in the Walking Index for Spinal Cord Injury (WISCI II) test,
timeFrame: tested monthly for at least 2 years postoperatively
measure: 10 meter walking test
timeFrame: tested monthly for at least 2 years postoperatively
measure: 2 minutes walking test
timeFrame: tested monthly for at least 2 years postoperatively
measure: time up and go test
timeFrame: tested monthly for at least 2 years postoperatively
measure: improvement measured by the spinal cord independence measure (SCIM III) test
timeFrame: tested monthly for at least 2 years postoperatively
measure: neurophysiological evidence of reconnection of fibers from motor origin
timeFrame: tested every 3 months for at least 2 years postoperatively
measure: neurophysiological evidence of reconnection of fibers from sensory origin
timeFrame: tested every 3 months for at least 2 years postoperatively
measure: neurophysiological evidence of reconnection of fibers from vegetative origin
timeFrame: tested every 3 months for at least 2 years postoperatively
measure: improvement of urination registered in the urodynamic study
timeFrame: tested every 3 months for at least 2 years postoperatively
measure: evidence regrowth of spinal cord fibers detected on MRI scans, evidence of functional reorganization of the brain detected in advanced MRI protocols; lack of tumorigenesis, spinal cord inflammation, progressive syringomyelia;
timeFrame: MRI imaging of the spinal cord and brain will be performed every 3 months in the first year and every 6 months in the second year
Other outcomes:
Locations:
city: Wroclaw
country: Poland
facility: Wroclaw Medical University
Study officials:
affiliation: Wroclaw Medical University
name: Pawel Tabakow, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tabakow P, Raisman G, Fortuna W, Czyz M, Huber J, Li D, Szewczyk P, Okurowski S, Miedzybrodzki R, Czapiga B, Salomon B, Halon A, Li Y, Lipiec J, Kulczyk A, Jarmundowicz W. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. 2014;23(12):1631-55. doi: 10.3727/096368914X685131. Epub 2014 Oct 21.
citation: Tabakow P, Jarmundowicz W, Czapiga B, Fortuna W, Miedzybrodzki R, Czyz M, Huber J, Szarek D, Okurowski S, Szewczyk P, Gorski A, Raisman G. Transplantation of autologous olfactory ensheathing cells in complete human spinal cord injury. Cell Transplant. 2013;22(9):1591-612. doi: 10.3727/096368912X663532.
citation: Collins A, Li D, Liadi M, Tabakow P, Fortuna W, Raisman G, Li Y. Partial Recovery of Proprioception in Rats with Dorsal Root Injury after Human Olfactory Bulb Cell Transplantation. J Neurotrauma. 2018 Jun 15;35(12):1367-1378. doi: 10.1089/neu.2017.5273. Epub 2018 Mar 29.
citation: Ibrahim A, Li D, Collins A, Tabakow P, Raisman G, Li Y. Comparison of olfactory bulbar and mucosal cultures in a rat rhizotomy model. Cell Transplant. 2014;23(11):1465-70. doi: 10.3727/096368913X676213. Epub 2013 Dec 30.
citation: Czyz M, Tabakow P, Hernandez-Sanchez I, Jarmundowicz W, Raisman G. Obtaining the olfactory bulb as a source of olfactory ensheathing cells with the use of minimally invasive neuroendoscopy-assisted supraorbital keyhole approach--cadaveric feasibility study. Br J Neurosurg. 2015 Jun;29(3):362-70. doi: 10.3109/02688697.2015.1006170. Epub 2015 Feb 7.
citation: Czyz M, Tabakow P, Gheek D, Mis M, Jarmundowicz W, Raisman G. The supraorbital keyhole approach via an eyebrow incision applied to obtain the olfactory bulb as a source of olfactory ensheathing cells--radiological feasibility study. Br J Neurosurg. 2014 Apr;28(2):234-40. doi: 10.3109/02688697.2013.817534. Epub 2013 Jul 19.