Spinal Cord InjuryNCT02870426
Collection and Characterisation of Human Olfactory Ensheathing Cells
An observational study of Spinal Cord Injury, run by St George's, University of London at 1 site in United Kingdom.
Trial summary
We aim to retrieve olfactory bulbs (OBs) from suitable human donors. We have defined two groups who will qualify: Group 1 - Deceased Donors: 1A: Donors after brainstem death (DBDs) undergoing solid organ donation 1B: Donors after brainstem death (DBDs) considered unsuitable for solid organ donation Group 2 - Living… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- Frontal Craniotomy and retrieval of OBs and OB Retrieval During Anterior Cranial Surgery
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Apr 2018to Jul 2023
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Deceased brain dead donors and living patients undergoing anterior cranial surgery in which the ON may be sacrificed as routine part of the procedure.
Who may be able to join
- Group 1 - Deceased Donors 1A
- Diagnosis of brainstem death, AND
- Consent from next of kin (NoK) for organ donation
- Consent from NoK for removal of olfactory bulbs (OBs)
- Coroner's consent for removal of OBs (when needed).
- 1B
Show all 14Show fewer
- Diagnosis of brainstem death, AND
- Contraindications for solid organ donation
- Consent from NoK for removal of OBs
- Coroners consent for removal of OBs (when needed)
- Group 2 - Living Donors
- Patients having anterior cranial surgery in which the ON may be cut or removed as part of the procedure.
- Consent from the operating surgeon to remove the OB of the corresponding ON in the event it is cut during the operation
- Consent from the patient for removal of the OB of the corresponding ON in the event it is cut during the operation
Who cannot join
- Children (<18 years old)
- Damage to anterior skull base including OBs
- Meningitis
- And applicable to group 2 only:
- Patients unable to consent for surgery
Trial locations and contacts
1 site in 1 country.
Florence Hogg, MBChB contact
United Kingdom1 site, 1 recruiting
- Recruiting
St George's Hospital
London, Tooting, SW17 0QT
About this study
We aim to retrieve olfactory bulbs (OBs) from suitable human donors. We have defined two groups who will qualify:
Group 1 - Deceased Donors:
Read more
1A: Donors after brainstem death (DBDs) undergoing solid organ donation
1B: Donors after brainstem death (DBDs) considered unsuitable for solid organ donation
Group 2 - Living Donors:
Neurosurgical patients undergoing anterior cranial surgery in which the olfactory nerve (ON) is cut as part of the surgical procedure. The OB of the concomitant severed ON would be donated.
We aim to optimise OB collection and Olfactory Ensheathing Cell (OEC) culture and storage. We will study the effects of patient diagnosis, age, cause of death (if applicable), co-morbidities and warm ischaemic time on cell survival and regenerative function.
In future studies we aim to store OECs in a GMP facility and transplant OECs into patients with spinal cord injuries.
Read the detailed description
Spinal cord injury (SCI) is a devastating condition. To date there is no treatment to improve outcome. There is limited regenerative capacity of the central nervous system (CNS), such that damaged neurons and severed axons are not replaced.
A substantial body of evidence suggests that olfactory ensheathing cells (OECs) obtained from olfactory bulbs (OBs) facilitate neuronal regeneration in rodents and humans with SCI. Indeed, transplanting autologous OECs from an OB into the injury site improved neurological outcome in a patient with SCI.
Harvesting autologous OBs to culture OECs has several disadvantages:
- If the OECs do not grow in vitro, the transplantation is abandoned;
- The retrieval procedure exposes a paralysed patient to the risks of craniotomy;
- Excising an OB can impair the sense of smell; and
- The number of OECs obtained is limited to one OB.
Investigators will collect human OECs from suitable donors which we have defined as two groups. Group 1 patients will be brain dead donors identified by the neuro-intensive care team as potential candidates for solid organ donation. The OBs will be retrieved as near to death as possible. Group 2 patients will be living donors undergoing elective neurosurgery in which the olfactory nerve is sacrificed as part of that procedure.
There are two OBs located at the anterior skull base, responsible for transmitting the sensation of smell from the nose to the brain. Obtaining OECs requires a craniotomy (opening the skull) to remove the OBs.
PHASE 1 will be divided into 2 stages. In stage 1 we will culture OECs and characterise them in the central laboratory. We aim to determine how the yield of OECs and their regenerative properties are affected by freeze-thaw, time left at room temperature and time left at 40C before culture as well as patient age. Each harvested sample will be transferred to the lab for further processing. Processing includes but is not limited to histological fixation, sectioning and staining, cell culture and storage. Some OECs will be frozen in liquid nitrogen to determine whether they can indeed be stored. In stage 2 we will transfer OECs outside St. George's to a GMP facility (to be determined). In the GMP facility, the OECs will be processed and stored according to the optimised conditions we have determined.
In PHASE 2, the OECs will be transplanted into patients with SCI.
- Conditions
- Spinal Cord Injury
- Being tested
- Frontal Craniotomy and retrieval of OBs, OB Retrieval During Anterior Cranial Surgery
- Keywords
- Olfactory ensheathing cells
- 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.
Frontal Craniotomy and retrieval of OBsProcedure or surgery
For Group 1A the craniotomy will occur during organ retrieval for transplantation under aseptic technique. For Group 1B it would occur as a separate surgical procedure prior to palliation under full asepsis.
OB Retrieval During Anterior Cranial SurgeryProcedure or surgery
Group 2: The patients routine anterior cranial surgery would proceed as planned without change to the surgical procedure. In the event that the ON had to be sacrificed for the purposes of surgery the OB of the concomitant nerve would be retrieved.
| Study group | Role | What they receive |
|---|---|---|
| Group 1A: | Donors after brainstem death (DBDs) undergoing solid organ donation Receives: Procedure: Frontal Craniotomy and retrieval of OBs | |
| Group 1B: | Donors after brainstem death (DBDs) considered unsuitable for solid organ donation Receives: Procedure: Frontal Craniotomy and retrieval of OBs | |
| Group 2: | Neurosurgical patients undergoing anterior cranial surgery in which the olfactory nerve (ON) is cut as part of the surgical procedure. The OB of the concomitant severed ON would be donated. Receives: Procedure: OB Retrieval During Anterior Cranial Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ability to culture olfactory ensheathing cells from human donors
Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
Measured: 10-15 days
Secondary outcomes (6)
Effect of cause of death for Group 1 donors
Plot of cause of death vs. Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
Measured: 10-15 days
Effect of patient age
Plot of patient age vs. Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
Measured: 10-15 days
Effect of freeze/thaw cycles
Plot of number of freeze/thaw cycles vs. Number of olfactory ensheathing cells cultured at days 10-15 in vitro.
Measured: 10-15 days
Effect of storage in liquid nitrogen
Plot of Number of olfactory ensheathing cells cultured at days 10-15 in vitro when cells are cultured fresh vs. after one week and one month storage in liquid nitrogen.
Measured: up to 1 month
Effect of time from extraction to culture at room temperature
Plot of time from extraction to culture vs. Number of olfactory ensheathing cells cultured.
Measured: 1 month
Effect of time from extraction to culture at 4 deg C
Plot of time from extraction to culture at 4 deg C vs. Number of olfactory ensheathing cells cultured.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2016 (estimated)
- Study start9 Apr 2018
- Primary completionJun 2021 (estimated)
- Study completionJul 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 InjuryStudies 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
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St George's, University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marios Papadopoulos, FRCS (SN), Principal investigator, St George's, University of LondonSamira Saadoun, PhD, Principal investigator, St George's, University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02870426
- Sponsor's protocol ID
- 16.0069
- Status last verified
- Mar 2018
- First submitted
- 26 Apr 2016
- Last updated
- 4 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 24007776Miedzybrodzki R, Tabakow P, Fortuna W, Czapiga B, Jarmundowicz W. The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells. Glia. 2006 Nov 1;54(6):557-65. doi: 10.1002/glia.20395.
PubMed 16917854Raisman G. Olfactory ensheathing cells and repair of brain and spinal cord injuries. Cloning Stem Cells. 2004;6(4):364-8. doi: 10.1089/clo.2004.6.364.
PubMed 15671664Li Y, Decherchi P, Raisman G. Transplantation of olfactory ensheathing cells into spinal cord lesions restores breathing and climbing. J Neurosci. 2003 Feb 1;23(3):727-31. doi: 10.1523/JNEUROSCI.23-03-00727.2003.
PubMed 12574399Keyvan-Fouladi N, Li Y, Raisman G. How do transplanted olfactory ensheathing cells restore function? Brain Res Brain Res Rev. 2002 Oct;40(1-3):325-7. doi: 10.1016/s0165-0173(02)00215-1.
PubMed 12589931Raisman G. Olfactory ensheathing cells - another miracle cure for spinal cord injury? Nat Rev Neurosci. 2001 May;2(5):369-75. doi: 10.1038/35072576.
PubMed 11331921
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Collection and Characterisation of Human Olfactory Ensheathing Cells
- ClinicalTrials.gov ID
- NCT02870426
- Acronym / sponsor ID
- 16.0069
- Conditions
- Spinal Cord Injury
- Keywords
- Olfactory ensheathing cells
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- St George's, University of LondonUniversity, hospital or other
- Study start
- 9 Apr 2018 (actual)
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Jul 2023 (estimated)
- First posted
- 17 Aug 2016 (estimated)
- 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.
We aim to retrieve olfactory bulbs (OBs) from suitable human donors. We have defined two groups who will qualify:
Group 1 - Deceased Donors:
1A: Donors after brainstem death (DBDs) undergoing solid organ donation
1B: Donors after brainstem death (DBDs) considered unsuitable for solid organ donation
Group 2 - Living Donors:
Neurosurgical patients undergoing anterior cranial surgery in which the olfactory nerve (ON) is cut as part of the surgical procedure. The OB of the concomitant severed ON would be donated.
We aim to optimise OB collection and Olfactory Ensheathing Cell (OEC) culture and storage. We will study the effects of patient diagnosis, age, cause of death (if applicable), co-morbidities and warm ischaemic time on cell survival and regenerative function.
In future studies we aim to store OECs in a GMP facility and transplant OECs into patients with spinal cord injuries.
Detailed description
Spinal cord injury (SCI) is a devastating condition. To date there is no treatment to improve outcome. There is limited regenerative capacity of the central nervous system (CNS), such that damaged neurons and severed axons are not replaced.
A substantial body of evidence suggests that olfactory ensheathing cells (OECs) obtained from olfactory bulbs (OBs) facilitate neuronal regeneration in rodents and humans with SCI. Indeed, transplanting autologous OECs from an OB into the injury site improved neurological outcome in a patient with SCI.
Harvesting autologous OBs to culture OECs has several disadvantages:
- If the OECs do not grow in vitro, the transplantation is abandoned;
- The retrieval procedure exposes a paralysed patient to the risks of craniotomy;
- Excising an OB can impair the sense of smell; and
- The number of OECs obtained is limited to one OB.
Investigators will collect human OECs from suitable donors which we have defined as two groups. Group 1 patients will be brain dead donors identified by the neuro-intensive care team as potential candidates for solid organ donation. The OBs will be retrieved as near to death as possible. Group 2 patients will be living donors undergoing elective neurosurgery in which the olfactory nerve is sacrificed as part of that procedure.
There are two OBs located at the anterior skull base, responsible for transmitting the sensation of smell from the nose to the brain. Obtaining OECs requires a craniotomy (opening the skull) to remove the OBs.
PHASE 1 will be divided into 2 stages. In stage 1 we will culture OECs and characterise them in the central laboratory. We aim to determine how the yield of OECs and their regenerative properties are affected by freeze-thaw, time left at room temperature and time left at 40C before culture as well as patient age. Each harvested sample will be transferred to the lab for further processing. Processing includes but is not limited to histological fixation, sectioning and staining, cell culture and storage. Some OECs will be frozen in liquid nitrogen to determine whether they can indeed be stored. In stage 2 we will transfer OECs outside St. George's to a GMP facility (to be determined). In the GMP facility, the OECs will be processed and stored according to the optimised conditions we have determined.
In PHASE 2, the OECs will be transplanted into patients with SCI.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1A: | – | Procedure: Frontal Craniotomy and retrieval of OBsDonors after brainstem death (DBDs) undergoing solid organ donation |
| Group 1B: | – | Procedure: Frontal Craniotomy and retrieval of OBsDonors after brainstem death (DBDs) considered unsuitable for solid organ donation |
| Group 2: | – | Procedure: OB Retrieval During Anterior Cranial SurgeryNeurosurgical patients undergoing anterior cranial surgery in which the olfactory nerve (ON) is cut as part of the surgical procedure. The OB of the concomitant severed ON would be donated. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Deceased brain dead donors and living patients undergoing anterior cranial surgery in which the ON may be sacrificed as routine part of the procedure.
Key inclusion criteria (14 listed)
- Group 1 - Deceased Donors 1A
- Diagnosis of brainstem death, AND
- Consent from next of kin (NoK) for organ donation
- Consent from NoK for removal of olfactory bulbs (OBs)
- Coroner's consent for removal of OBs (when needed).
Key exclusion criteria (5 listed)
- Children (<18 years old)
- Damage to anterior skull base including OBs
- Meningitis
- Patients unable to consent for surgery
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 |
|---|---|---|
| Frontal Craniotomy and retrieval of OBsFor Group 1A the craniotomy will occur during organ retrieval for transplantation under aseptic technique. For Group 1B it would occur as a separate surgical procedure prior to palliation under full asepsis. | Procedure or surgery | Group 1A:, Group 1B: |
| OB Retrieval During Anterior Cranial SurgeryGroup 2: The patients routine anterior cranial surgery would proceed as planned without change to the surgical procedure. In the event that the ON had to be sacrificed for the purposes of surgery the OB of the concomitant nerve would be retrieved. | Procedure or surgery | Group 2: |
Primary outcome
Ability to culture olfactory ensheathing cells from human donors
Time frame: 10-15 days
Number of olfactory ensheathing cells cultured per olfactory bulb at days 10-15 in vitro.
6 secondary outcomes
Effect of cause of death for Group 1 donors
Time frame: 10-15 days
Effect of patient age
Time frame: 10-15 days
Effect of freeze/thaw cycles
Time frame: 10-15 days
Effect of storage in liquid nitrogen
Time frame: up to 1 month
Effect of time from extraction to culture at room temperature
Time frame: 1 month
Effect of time from extraction to culture at 4 deg C
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2018.
- Results publication: 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.
- Results publication: PubMed 16917854Miedzybrodzki R, Tabakow P, Fortuna W, Czapiga B, Jarmundowicz W. The olfactory bulb and olfactory mucosa obtained from human cadaver donors as a source of olfactory ensheathing cells. Glia. 2006 Nov 1;54(6):557-65. doi: 10.1002/glia.20395.
- Results publication: PubMed 15671664Raisman G. Olfactory ensheathing cells and repair of brain and spinal cord injuries. Cloning Stem Cells. 2004;6(4):364-8. doi: 10.1089/clo.2004.6.364.
- Results publication: PubMed 12574399Li Y, Decherchi P, Raisman G. Transplantation of olfactory ensheathing cells into spinal cord lesions restores breathing and climbing. J Neurosci. 2003 Feb 1;23(3):727-31. doi: 10.1523/JNEUROSCI.23-03-00727.2003.
- Results publication: PubMed 12589931Keyvan-Fouladi N, Li Y, Raisman G. How do transplanted olfactory ensheathing cells restore function? Brain Res Brain Res Rev. 2002 Oct;40(1-3):325-7. doi: 10.1016/s0165-0173(02)00215-1.
- Results publication: PubMed 11331921Raisman G. Olfactory ensheathing cells - another miracle cure for spinal cord injury? Nat Rev Neurosci. 2001 May;2(5):369-75. doi: 10.1038/35072576.
- Individual participant dataSharing planned: No
Related trials for Spinal Cord Injury
Recruiting
MyHand-SCI: An Active Hand Orthosis for Spinal Cord Injury
Spinal Cord Injuries, Tetraplegia
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)
Recruiting
Transcutaneous Spinal Cord Stimulation Combined With 4-Aminopyridine and Intensive Rehabilitation in SCI
Spinal Cord Injuries
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
A Trial Investigating the Efficacy and Safety of NVG-291 in Subjects With Chronic Spinal Cord Injury
Chronic Spinal Cord Injury
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.
Florence Hogg, MBChB contact
Marios Papadopoulos, FRCS (SN) principal investigator
St George's, University of London
Samira Saadoun, PhD principal investigator
St George's, University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Cord Injury, run by St George's, University of London at 1 site in United Kingdom.
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 14 inclusion and 5 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 4 May 2018. 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 United Kingdom. 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.
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 Marios Papadopoulos, FRCS (SN) (02087254179, mpapadop@sgul.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ability to culture olfactory ensheathing cells from human donors (time frame: 10-15 days). 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 NCT02870426, 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 4 May 2018.