Collection and Characterisation of Human Olfactory Ensheathing Cells

NCT ID: NCT02870426

Last Updated: 2018-05-04

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

Total Enrollment

50 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-04-09

Study Completion Date

2023-07-31

Brief Summary

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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

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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:

1. If the OECs do not grow in vitro, the transplantation is abandoned;
2. The retrieval procedure exposes a paralysed patient to the risks of craniotomy;
3. Excising an OB can impair the sense of smell; and
4. 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

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Spinal Cord Injury

Study Design

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Observational Model Type

OTHER

Study Time Perspective

OTHER

Study Groups

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Group 1A:

Donors after brainstem death (DBDs) undergoing solid organ donation

Frontal Craniotomy and retrieval of OBs

Intervention Type PROCEDURE

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.

Group 1B:

Donors after brainstem death (DBDs) considered unsuitable for solid organ donation

Frontal Craniotomy and retrieval of OBs

Intervention Type PROCEDURE

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.

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.

OB Retrieval During Anterior Cranial Surgery

Intervention Type PROCEDURE

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.

Interventions

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Frontal Craniotomy and retrieval of OBs

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.

Intervention Type PROCEDURE

OB Retrieval During Anterior Cranial 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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

Group 1 - Deceased Donors 1A

1. Diagnosis of brainstem death, AND
2. Consent from next of kin (NoK) for organ donation
3. Consent from NoK for removal of olfactory bulbs (OBs)
4. Coroner's consent for removal of OBs (when needed).

1B

1. Diagnosis of brainstem death, AND
2. Contraindications for solid organ donation
3. Consent from NoK for removal of OBs
4. Coroners consent for removal of OBs (when needed)

Group 2 - Living Donors

1. Patients having anterior cranial surgery in which the ON may be cut or removed as part of the procedure.
2. Consent from the operating surgeon to remove the OB of the corresponding ON in the event it is cut during the operation
3. Consent from the patient for removal of the OB of the corresponding ON in the event it is cut during the operation

Exclusion Criteria

1. Children (\<18 years old)
2. Damage to anterior skull base including OBs
3. Meningitis

And applicable to group 2 only:

Patients unable to consent for surgery
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St George's, University of London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marios Papadopoulos, FRCS (SN)

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Samira Saadoun, PhD

Role: PRINCIPAL_INVESTIGATOR

St George's, University of London

Locations

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St George's Hospital

London, Tooting, United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Marios Papadopoulos, FRCS (SN)

Role: CONTACT

02087254179

Florence Hogg, MBChB

Role: CONTACT

References

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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 RESULT
PMID: 24007776 (View on PubMed)

Miedzybrodzki 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.

Reference Type RESULT
PMID: 16917854 (View on PubMed)

Raisman 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.

Reference Type RESULT
PMID: 15671664 (View on PubMed)

Li 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.

Reference Type RESULT
PMID: 12574399 (View on PubMed)

Keyvan-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.

Reference Type RESULT
PMID: 12589931 (View on PubMed)

Raisman G. Olfactory ensheathing cells - another miracle cure for spinal cord injury? Nat Rev Neurosci. 2001 May;2(5):369-75. doi: 10.1038/35072576.

Reference Type RESULT
PMID: 11331921 (View on PubMed)

Study Documents

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Document Type: Individual Participant Data Set

The project documents will be available directly from the research team. Please e-mail Dr Florence Hogg [email protected]

View Document

Other Identifiers

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16.0069

Identifier Type: -

Identifier Source: org_study_id

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