Autologous Bulbar Olfactory Ensheathing Cells and Nerve Grafts for Treatment of Patients With Spinal Cord Transection

NCT ID: NCT03933072

Last Updated: 2021-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-01

Study Completion Date

2023-03-01

Brief Summary

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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

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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.

Conditions

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Spinal Cord Injury at C5-Th10 Level With Complete Lesion Spinal Cord Transection

Keywords

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complete spinal cord injury, spinal cord transection, olfactory ensheathing cells, olfactory fibroblasts, Glial Neuropatch, nerve grafts

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

interventional study, parallel assessment, open label, non-randomized, safety-efficacy study; sponsored clinical trial;
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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patients with complete spinal cord injury

the planned interventions have been described in the section below

Group Type EXPERIMENTAL

obtaining of autologous human olfactory bulb, autologous sural nerve preparation

Intervention Type PROCEDURE

The operative procedure will be aimed to obtain one of the patient's olfactory bulbs. The operation will be performed using a minimally invasive intracranial microsurgical endoscopy-assisted or transnasal endoscopic approach. During the same operation the patient sural nerve will be prepared for a future grafting.

production of Glial Neuropatch

Intervention Type BIOLOGICAL

The human autologous olfactory ensheathing glia and olfactory fibroblast isolated from the olfactory bulb will be used for production of Glial Neuropatch in a laboratory facility in accordance with 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).

microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges

Intervention Type PROCEDURE

The surgery will consists of laminectomy/laminotomy, midline durotomy above the area of spinal cord lesion, detethering of the spinal cord from fibrotic 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.

Interventions

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obtaining of autologous human olfactory bulb, autologous sural nerve preparation

The operative procedure will be aimed to obtain one of the patient's olfactory bulbs. The operation will be performed using a minimally invasive intracranial microsurgical endoscopy-assisted or transnasal endoscopic approach. During the same operation the patient sural nerve will be prepared for a future grafting.

Intervention Type PROCEDURE

production of Glial Neuropatch

The human autologous olfactory ensheathing glia and olfactory fibroblast isolated from the olfactory bulb will be used for production of Glial Neuropatch in a laboratory facility in accordance with 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).

Intervention Type BIOLOGICAL

microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges

The surgery will consists of laminectomy/laminotomy, midline durotomy above the area of spinal cord lesion, detethering of the spinal cord from fibrotic 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.

Intervention Type PROCEDURE

Eligibility Criteria

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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!
Minimum Eligible Age

16 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wroclaw Medical University

OTHER

Sponsor Role collaborator

Akson, Neuro-Rehabilitation Center for the Treatment of Spinal Cord Injuries

UNKNOWN

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Poznan University of Medical Sciences

OTHER

Sponsor Role collaborator

Nicholls Spinal Injury Foundation

OTHER

Sponsor Role lead

Responsible Party

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Dr. Pawel Tabakow

Ass. Professor, MD PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Pawel Tabakow, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Wroclaw Medical University

Locations

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Wroclaw Medical University

Wroclaw, , Poland

Site Status RECRUITING

Countries

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Poland

Central Contacts

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Pawel Tabakow, MD PhD

Role: CONTACT

Phone: 0048717343400

Email: [email protected]

Facility Contacts

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Pawel Tabakow, MD PhD

Role: primary

Aleksandra Nowak, Dr

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 25338642 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24007776 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29285976 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24380436 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25659961 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23869574 (View on PubMed)

Other Identifiers

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Wroclaw Walk Again Project

Identifier Type: -

Identifier Source: org_study_id