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
Condition or disease | Intervention/treatment | Phase |
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Spinal Cord Injury at C5-Th10 Level With Complete Lesion Spinal Cord Transection | 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 | Phase 1 Phase 2 |
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 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).
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 Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 2 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | interventional study, parallel assessment, open label, non-randomized, safety-efficacy study; sponsored clinical trial; |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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. |
Actual Study Start Date : | March 2016 |
Estimated Primary Completion Date : | March 1, 2021 |
Estimated Study Completion Date : | March 1, 2022 |
Arm | Intervention/treatment |
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Experimental: patients with complete spinal cord injury
the planned interventions have been described in the section below
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Procedure: 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.
Biological: 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).
Procedure: 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.
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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.
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
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)
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
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
Flexor spasms are rated on a 4 point scale that ranges from:
0 No reaction
SCATS extensor spasms assessment 0 No reaction
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).
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.
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.
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.
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.
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.
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.
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
Ages Eligible for Study: | 16 Years to 65 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Note: All patients wanting to participate in this study have to send their application via the walk-again-project.org recruitment website!
Contact: Pawel Tabakow, MD PhD | 0048717343400 | p.tabakov@wp.pl |
Poland | |
Wroclaw Medical University | Recruiting |
Wroclaw, Poland, 50-556 | |
Contact: Pawel Tabakow, MD PhD 0048717343400 p.tabakov@wp.pl | |
Contact: Aleksandra Nowak, Dr 0048 71 784 14 92 ale.nowak@umed.wroc.pl | |
Principal Investigator: Pawel Tabakow, MD PhD |
Principal Investigator: | Pawel Tabakow, MD PhD | Wroclaw Medical University |
Tracking Information | |||||
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First Submitted Date ICMJE | April 24, 2019 | ||||
First Posted Date ICMJE | May 1, 2019 | ||||
Last Update Posted Date | May 9, 2019 | ||||
Actual Study Start Date ICMJE | March 2016 | ||||
Estimated Primary Completion Date | March 1, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Autologous Bulbar Olfactory Ensheathing Cells and Nerve Grafts for Treatment of Patients With Spinal Cord Transection | ||||
Official Title ICMJE | 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. | ||||
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 |
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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 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). 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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: interventional study, parallel assessment, open label, non-randomized, safety-efficacy study; sponsored clinical trial; Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: patients with complete spinal cord injury
the planned interventions have been described in the section below
Interventions:
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
2 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | March 1, 2022 | ||||
Estimated Primary Completion Date | March 1, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
Note: All patients wanting to participate in this study have to send their application via the walk-again-project.org recruitment website! |
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Sex/Gender ICMJE |
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Ages ICMJE | 16 Years to 65 Years (Child, Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Poland | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03933072 | ||||
Other Study ID Numbers ICMJE | Wroclaw Walk Again Project | ||||
Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | Dr. Pawel Tabakow, Wroclaw Medical University | ||||
Study Sponsor ICMJE | Nicholls Spinal Injury Foundation | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Nicholls Spinal Injury Foundation | ||||
Verification Date | April 2019 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |