Clinical trial NCT02870426: Collection and Characterisation of Human Olfactory Ensheathing Cells
Official title: Collection and Characterisation of Human Olfactory Ensheathing Cells
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Spinal Cord Injury
Keywords: Olfactory ensheathing cells
Lead sponsor: St George's, University of London
Sponsor class: OTHER
First posted: 2016-08-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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 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:

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.

Eligibility criteria: 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

Primary outcomes:
measure: Ability to culture olfactory ensheathing cells from human donors
timeFrame: 10-15 days
Secondary outcomes:
measure: Effect of cause of death for Group 1 donors
timeFrame: 10-15 days
measure: Effect of patient age
timeFrame: 10-15 days
measure: Effect of freeze/thaw cycles
timeFrame: 10-15 days
measure: Effect of storage in liquid nitrogen
timeFrame: up to 1 month
measure: Effect of time from extraction to culture at room temperature
timeFrame: 1 month
measure: Effect of time from extraction to culture at 4 deg C
timeFrame: 1 month
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St George's Hospital
state: Tooting
Study officials:
affiliation: St George's, University of London
name: Marios Papadopoulos, FRCS (SN)
role: PRINCIPAL_INVESTIGATOR
affiliation: St George's, University of London
name: Samira Saadoun, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.