Spinal Cord Injury at C5-Th10 Level With Complete LesionPhase 1/2NCT03933072
Autologous Bulbar Olfactory Ensheathing Cells and Nerve Grafts for Treatment of Patients With Spinal Cord Transection
A Phase 1/2 study testing obtaining of autologous human olfactory bulb, autologous sural nerve preparation, production of Glial Neuropatch and microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges in people with Spinal Cord Injury at C5-Th10 Level With Complete Lesion and Spinal Cord Transection, run by Nicholls Spinal Injury Foundation at 1 site in Poland.
Trial 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… Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Spinal Cord Injury at C5-Th10 Level With Complete Lesion, Spinal Cord Transection
- What is being tested?
- obtaining of autologous human olfactory bulb, autologous sural nerve preparation, production of Glial Neuropatch and microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 sitePoland
- Study dates
- 1 Mar 2016to 1 Mar 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- A single spinal cord injury between vertebral levels C5-Th10 with a total anatomic disruption of continuity.
- Myelopathy not exceeding 2 spinal cord segments as confirmed by MRI.
- 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)
- Age from 16 to 65 years.
- Patient undergoing continuous rehabilitation.
- Good patient motivation and cooperation, no mental disturbances.
- Patient is ready to stay with an accompanying person for at least 3 years in Poland.
- Patient without cardiac disease and without epilepsy, does not have peacemaker or any electronic or ferromagnetic implants.
Who cannot join
- A coexisting lesion of the nervous system.
- Progressive post-traumatic syringomyelia.
- Significant spinal stenosis or instability.
- Muscle atrophy or joint ossifications.
- Severe systemic disease such as neoplasm, contagious disease, diabetes etc.
- Chronic sinusitis destroying the paranasal sinuses, tumors of nasal cavities or patients with hyposmia in repetitive smell perception tests will be excluded.
- 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!
Trial locations and contacts
1 site in 1 country.
Poland1 site, 1 recruiting
- Recruiting
Wroclaw Medical University
Wroclaw, 50-556
Pawel Tabakow, MD PhD, 0048717343400, p.tabakov@wp.pl
Aleksandra Nowak, Dr, 0048 71 784 14 92, ale.nowak@umed.wroc.pl
About this study
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.
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
Read the 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.
- Being tested
- obtaining of autologous human olfactory bulb, autologous sural nerve preparation, production of Glial Neuropatch, microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges
- Keywords
- complete spinal cord injury, spinal cord transection, olfactory ensheathing cells, olfactory fibroblasts, Glial Neuropatch, nerve grafts
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
obtaining of autologous human olfactory bulb, autologous sural nerve preparationProcedure or surgery
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 NeuropatchBiological
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 bridgesProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| patients with complete spinal cord injury | Experimental | the planned interventions have been described in the section below Receives: Procedure: obtaining of autologous human olfactory bulb, autologous sural nerve preparation; Biological: production of Glial Neuropatch; Procedure: microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges |
What is being measured
The primary outcome is the main question the study is designed to answer.
improvement of the neurologic state measured by the American Spinal Injury Association (ASIA) score.
A positive outcome will be defined as any detectable improvement of motor and /or sensory function below the level of spinal cord injury, that will result that the patient will change from being with complete spinal cord injury (assigned as ASIA A) to incomplete (ASIA B,C,D or E). ASIA E means complete recovery from spinal cord injury-no clinical evidence of neurological impairment.
Measured: up to 2 years postoperatively
improvement of the strenght of trunk muscles measured by the Berg Balance scale
a set of tests evaluating the risk of patient to fall during sitting, standing and transfers
The results from the specific tests assign the patients to the following three groups:
41-56 points = low fall risk; 21-40 pts. = medium fall risk, 0 -20 pts. = high fall risk
An improvement of the trunk muscle strenght that will transfer the patient from the high fall risk group to the medium or low fall risk group will be considered as essential clinical improvement.
Measured: up to 2 years postoperatively
improvement of neurologic state measured with tests of deep sensation
deep pressure tests applied to the specific dermatomal areas,0 points means no deep sensation while 1 point means sensation of same feeling when pressure is applied
Measured: up to 2 years postoperatively
improvement of neurologic state measured with tests of vibration
vibration tests applied on the shoulder, elbow, wrist,finger,knee,malleolus and toe
0 Zero, A Diminished, B More vague description - less accurate than A, C Causalgia, 2 Normal
Measured: up to 2 years postoperatively
improvement of neurologic state measured with tests of joint position sense
joint position test applied on the wrist, thumb, little finger, knee, ankle and great toe
0 points- absence of joint position sense (during 8 of 10 or more attempts)
- point- impaired sense (correct only on large movements of the joint during 8 of 10 attempts, and incorrect on small movements of the joint (8 of 10 or more attempts)
- points- normal sense (during 8 of 10 or more attempts) on small and large movements;
Measured: up to 2 years postoperatively
Secondary outcomes (12)
decrease of muscle spasticity for at least 1 level measured the Ashworth scale
The 5 level spasticity Ashworth scale includes:
level 0- no increase in muscle tone, level 1- slight increase in muscle tone, manifested by a catch and release or by minimal, resistance at the end of the range of movement (ROM) when the affected part(s) is moved in flexion or extension, level 2-slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the reminder (less than half) of the ROM, level 3-more marked increase in muscle tone throughout most of the ROM but affected part(s) easily moved, level 4-considerable increase in muscle tone passive, movement difficult, level 5-affected part(s) rigid in flexion or extension
Measured: tested monthly for at least 2 years postoperatively
Spinal Cord Assessment Tool for Spastic Reflexes ( SCATS)
a test evaluating the clonus rate, and the rate of flexors and extensor muscle spasms
Clonus is rated on a 4 point scale that ranges from:
0 No reaction
- Mild lasting <3sec
- Moderate lasting 3-10 seconds
- Severe lasting > 10 seconds
Flexor spasms are rated on a 4 point scale that ranges from:
0 No reaction
- Mild, less than 10 degrees of excursion in flexion at knee and hip, or extension of the great toe
- Moderate = 10-30 degrees of flexion at knee and hip
- Severe with >30 degrees of hip and knee flexion
SCATS extensor spasms assessment 0 No reaction
- Mild lasting <3sec
- Moderate lasting 3-10 seconds
- Severe lasting > 10 seconds
Test interpretation: The better the patient improvement is, the lower points he will be assigned, reaching at the end the ideal state of being without clonus and muscle spasms (0 points).
Measured: tested monthly for at least 2 years postoperatively
improvement of locomotion ability in the Walking Index for Spinal Cord Injury (WISCI II) test,
The WISCI II test assesses the patient walking ability from being unable to walk (0 level) to being able to walk normally without any help (level 20).
Interpretation of the test: Any patient improvement that will assign him to a higher level of walking independency compared to the preoperative state will be considered as positive outcome.
Measured: tested monthly for at least 2 years postoperatively
10 meter walking test
a test measuring the velocity of walking the distance of 10 meters; (only the middle 6 meters are timed);
Any improvement of the ambulation velocity will be considered as positive outcome.
Measured: tested monthly for at least 2 years postoperatively
2 minutes walking test
a test measuring the distance ambulated in 2 minutes [m]
Any improvement of the distance of ambulation in the period of 2 minutes will be considered as positive outcome.
Measured: tested monthly for at least 2 years postoperatively
time up and go test
The patient should sit on a standard arm chair, placing his/her back against the chair and resting his/her arms chair's arms. Any assistive device used for walking should be nearby. Regular footwear and customary walking aids should be used. The patient should walk to a line that is 3 meters (9.8 feet) away, turn around at the line, walk back to the chair, and sit down.
Any decrease of the time needed for completion of this test will be considered as positive outcome.
Measured: tested monthly for at least 2 years postoperatively
improvement measured by the spinal cord independence measure (SCIM III) test
improvement of the patient self care ability
Measured: tested monthly for at least 2 years postoperatively
neurophysiological evidence of reconnection of fibers from motor origin
a set of tests evaluating the conductivity of efferent central and peripheral nerve fibers and the muscle response to electrical stimulation, including motor evoked potentials (MEP), electromyography (EMG) and electroneurography (ENG),
Measured: tested every 3 months for at least 2 years postoperatively
neurophysiological evidence of reconnection of fibers from sensory origin
the electrical perceptual thresholding (EPT) test- evaluating the dermatomal sensation of the upper and lower limbs in the condition of low voltage current application (from 0 to 7-8 mA)
Interpretation of the test: any tingling sensation reported by the patient in the previously anesthetic dermatomes, in the condition of current below 4 mA will be considered as essential improvement of skin sensation.
Measured: tested every 3 months for at least 2 years postoperatively
neurophysiological evidence of reconnection of fibers from vegetative origin
skin sympathetic response (SSR)
Electrophysiological study assessing the integrity of the supraspinal autonomic pathways. Is performed on the median and tibial nerves.
Test interpretation: any positive vegetative response in the tested paralyzed limbs that was previously absent will be considered as positive outcome.
Measured: tested every 3 months for at least 2 years postoperatively
improvement of urination registered in the urodynamic study
a test measuring the electrophysiological activity of the bladder muscles and the bladder sensation
Test interpretation: Any evidence of bladder detrusor -urethral sphincter synergy, together with the evidence of improved urination will be considered as positive outcome
Measured: tested every 3 months for at least 2 years postoperatively
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;
evidence of spinal cord fiber reconstitution and brain center reorganization detected on MRI scans, including advanced imaging techniques
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start1 Mar 2016
- Primary completion1 Mar 2023 (estimated)
- Study completion1 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Spinal Cord Injury at C5-Th10 Level With Complete LesionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- interventional study, parallel assessment, open label, non-randomized, safety-efficacy study; sponsored clinical trial;
- Masking
- None (open label)
- Enrolment
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nicholls Spinal Injury Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- Wroclaw Medical University, Akson, Neuro-Rehabilitation Center for the Treatment of Spinal Cord Injuries, University College, London, Poznan University of Medical Sciences
- Responsible party
- Principal investigator, Dr. Pawel Tabakow, Wroclaw Medical University
- Investigators
- Pawel Tabakow, MD PhD, Principal investigator, Wroclaw Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03933072
- Sponsor's protocol ID
- Wroclaw Walk Again Project
- Status last verified
- Nov 2021
- First submitted
- 24 Apr 2019
- Last updated
- 23 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25338642Tabakow 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.
PubMed 24007776Collins 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.
PubMed 29285976Ibrahim 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.
PubMed 24380436Czyz 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.
PubMed 25659961Czyz 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.
PubMed 23869574
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03933072
- Acronym / sponsor ID
- Wroclaw Walk Again Project
- Keywords
- complete spinal cord injury, spinal cord transection, olfactory ensheathing cells, olfactory fibroblasts, Glial Neuropatch, nerve grafts
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2 participants (estimated)
- Lead sponsor
- Nicholls Spinal Injury FoundationUniversity, hospital or other
- Collaborators
- Wroclaw Medical University, Akson, Neuro-Rehabilitation Center for the Treatment of Spinal Cord Injuries, University College, London, Poznan University of Medical Sciences
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 1 Mar 2023 (estimated)
- Study completion
- 1 Mar 2023 (estimated)
- First posted
- 1 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- interventional study, parallel assessment, open label, non-randomized, safety-efficacy study; sponsored clinical trial;
| Arm | Type | Receives |
|---|---|---|
| patients with complete spinal cord injury | Experimental | Procedure: obtaining of autologous human olfactory bulb, autologous sural nerve preparation, Biological: production of Glial Neuropatch, Procedure: microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridgesthe planned interventions have been described in the section below |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- A single spinal cord injury between vertebral levels C5-Th10 with a total anatomic disruption of continuity.
- Myelopathy not exceeding 2 spinal cord segments as confirmed by MRI.
- 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)
- Age from 16 to 65 years.
- Patient undergoing continuous rehabilitation.
Key exclusion criteria (8 listed)
- A coexisting lesion of the nervous system.
- Progressive post-traumatic syringomyelia.
- Significant spinal stenosis or instability.
- Muscle atrophy or joint ossifications.
- Severe systemic disease such as neoplasm, contagious disease, diabetes etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| obtaining of autologous human olfactory bulb, autologous sural nerve preparationThe 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. | Procedure or surgery | patients with complete spinal cord injury |
| production of Glial NeuropatchThe 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). | Biological | patients with complete spinal cord injury |
| microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridgesThe 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. | Procedure or surgery | patients with complete spinal cord injury |
Primary outcome
improvement of the neurologic state measured by the American Spinal Injury Association (ASIA) score.
Time frame: up to 2 years postoperatively
A positive outcome will be defined as any detectable improvement of motor and /or sensory function below the level of spinal cord injury, that will result that the patient will change from being with complete spinal cord injury (assigned as ASIA A) to incomplete (ASIA B,C,D or E). ASIA E means complete recovery from spinal cord injury-no clinical evidence of neurological impairment.
improvement of the strenght of trunk muscles measured by the Berg Balance scale
Time frame: up to 2 years postoperatively
a set of tests evaluating the risk of patient to fall during sitting, standing and transfers The results from the specific tests assign the patients to the following three groups: 41-56 points = low fall risk; 21-40 pts. = medium fall risk, 0 -20 pts. = high fall risk An improvement of the trunk muscle strenght that will transfer the patient from the high fall risk group to the medium or low fall risk group will be considered as essential clinical improvement.
improvement of neurologic state measured with tests of deep sensation
Time frame: up to 2 years postoperatively
deep pressure tests applied to the specific dermatomal areas,0 points means no deep sensation while 1 point means sensation of same feeling when pressure is applied
improvement of neurologic state measured with tests of vibration
Time frame: up to 2 years postoperatively
vibration tests applied on the shoulder, elbow, wrist,finger,knee,malleolus and toe 0 Zero, A Diminished, B More vague description - less accurate than A, C Causalgia, 2 Normal
improvement of neurologic state measured with tests of joint position sense
Time frame: up to 2 years postoperatively
joint position test applied on the wrist, thumb, little finger, knee, ankle and great toe 0 points- absence of joint position sense (during 8 of 10 or more attempts) 1. point- impaired sense (correct only on large movements of the joint during 8 of 10 attempts, and incorrect on small movements of the joint (8 of 10 or more attempts) 2. points- normal sense (during 8 of 10 or more attempts) on small and large movements;
12 secondary outcomes
decrease of muscle spasticity for at least 1 level measured the Ashworth scale
Time frame: tested monthly for at least 2 years postoperatively
Spinal Cord Assessment Tool for Spastic Reflexes ( SCATS)
Time frame: tested monthly for at least 2 years postoperatively
improvement of locomotion ability in the Walking Index for Spinal Cord Injury (WISCI II) test,
Time frame: tested monthly for at least 2 years postoperatively
10 meter walking test
Time frame: tested monthly for at least 2 years postoperatively
2 minutes walking test
Time frame: tested monthly for at least 2 years postoperatively
time up and go test
Time frame: tested monthly for at least 2 years postoperatively
improvement measured by the spinal cord independence measure (SCIM III) test
Time frame: tested monthly for at least 2 years postoperatively
neurophysiological evidence of reconnection of fibers from motor origin
Time frame: tested every 3 months for at least 2 years postoperatively
neurophysiological evidence of reconnection of fibers from sensory origin
Time frame: tested every 3 months for at least 2 years postoperatively
neurophysiological evidence of reconnection of fibers from vegetative origin
Time frame: tested every 3 months for at least 2 years postoperatively
improvement of urination registered in the urodynamic study
Time frame: tested every 3 months for at least 2 years postoperatively
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;
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2021.
- Background: PubMed 25338642Tabakow 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.
- Background: PubMed 24007776Tabakow 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.
- Background: PubMed 29285976Collins 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.
- Background: PubMed 24380436Ibrahim 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.
- Background: PubMed 25659961Czyz 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.
- Background: PubMed 23869574Czyz 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pawel Tabakow, MD PhD principal investigator
Wroclaw Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing obtaining of autologous human olfactory bulb, autologous sural nerve preparation, production of Glial Neuropatch and microsurgical reconstruction of the transected spinal cord with autologous Glial Neuropatch-nerve bridges in people with Spinal Cord Injury at C5-Th10 Level With Complete Lesion and Spinal Cord Transection, run by Nicholls Spinal Injury Foundation at 1 site in Poland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pawel Tabakow, MD PhD (0048717343400, p.tabakov@wp.pl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
improvement of the neurologic state measured by the American Spinal Injury Association (ASIA) score. (time frame: up to 2 years postoperatively). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03933072, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2021.