Olfactory Cell Transplantation and Intensive Rehabilitati... | NCT07596563

NCT07596563

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Brief Summary

This is a randomised, blinded and controlled Phase I trial to measure the safety, feasibility and efficacy of a combined cell transplantation and intensive rehabilitation intervention to treat spinal cord injury. The trial aims to examine whether transplantation of olfactory cell nerve bridges combined with intensive rehabilitation is safe and feasible for people living with chronic spinal cord injury in Australia, and whether the intervention improves structural integrity of the spinal cord, functional recovery, overall health, and social wellbeing.

For the olfactory cell nerve bridge transplant, cells from inside the patient's own nose will be purified and engrafted as 3D cellular nerve bridges. Participants will receive a dose that is dependent on the size of the accessible space within the injury site of the spinal cord with up to 60 million cells being engrafted. The surgery for the transplantation will be performed by a neurosurgeon in which the spinal cord will be exposed to enable the nerve bridges to be placed into the injury site. The duration of the procedure will be 3-4 hours. Surgical notes will be used to monitor adherence to the protocol.

For intensive exercise rehabilitation, the intervention will be supervised and provided by physiotherapists and exercise physiologists at a for-purpose neurorehabilitation facility. The mode of administration will be one-on-one sessions. The 12- and 32-week rehabilitation programs will consist of up to 3 hours per day at the rehabilitation service providers, for 5 days per week. Participants will attend the provider that is within their geographical area. Over each week, sessions will involve a range and mix of activities which could include, but are not limited to, standing, gait training, upper limb strength, trunk stability/core strength, and aerobic training. Throughout the trial, logs of exercise activities will be completed by the participants and staff at the neurorehabilitation gyms. Rehabilitation will start from day 1 of the priming rehabilitation (PR) program and go for 12 weeks, then surgery and cell transplantation will occur at week 1 of the cell transplantation surgery and recover program which is 2 weeks post conclusion of Priming Rehabilitation (PR), followed by 5 weeks of recovery.

Rehabilitation is for 32 weeks starting 6 weeks post transplant surgery. Regenerative rehabilitation program is from weeks 1-32 of the regenerative rehabilitation (RR) program.

If nerve bridge production fails for whatever reason in the weeks prior to surgery, this will start an extension/contingency/alternative timeline, where a new nasal biopsy will need to be taken from the participant (along with accompanying tests). The cells will be grown up over the next 4 weeks with an additional week of nerve bridge production, while the participant engages in a further five weeks of priming rehabilitation.

Label	Type	Description	Intervention Names
Treatment group of cell and rehabilitation	Active Comparator	20 participants will be recruited	Biological: Olfactory Ensheathing Cell, biological intervention
Control Rehabilitation only group	Active Comparator	10 participants will be recruited	Other: rehabilitation

Name	Type	Description	Arm Group Labels	Other Names
Olfactory Ensheathing Cell, biological intervention	Biological	Treatment group of cell transplantation and rehabilitation	Treatment group of cell and rehabilitation

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Recruitment feasibility. Feasibility of delivering a cell therapy intervention and associated rehabilitation program in terms of recruitment rate - i.e. willingness of participants to complete the full program. This is a composite primary outcome.		3 weeks after completion of full intervention (Regenerative Rehab (RR) week 32 of Regenerative Rehabilitation Program) i.e. at RR week 35 (post commencement of Regenerative Rehabilitation Program)
Safety Ratings. This Outcome and assessment is of safety in general, so it encompasses all AEs and SAEs and so is a composite primary outcome.		3 weeks after completion of full intervention (Regenerative Rehab (RR) week 32 of Regenerative Rehabilitation Program) i.e. at RR week 35 (post commencement of Regenerative Rehabilitation Program)
Safety of transplantation: measured by adverse anatomical changes to the injury/transplant site using quantitative MRI measures.		MRI/FA-DTI measured at week 0 (the week prior to start of priming rehab (PR)), week 13 of PR, at week 0 of regenerative rehab (RR), RR week 7, RR week 20, RR week 33.

Secondary Outcomes

Measure	Description	Time Frame
4a. Changes in AIS grade		Outcome measured at screening, then week Priming Rehabilitation (PR) week 13, Regenerative Rehab(RR) week 7, RR week 20, RR week 33 (i.e. 33 weeks post-commencement of Regenerative Rehabilitation intervention
Changes in electrophysiological assessments - somatosensory evoked potentials (SSEP)

Eligibility Module

Eligibility Criteria

Inclusion/exclusion criteria for participants have been determined in consultation with medical and rehabilitation specialists including a clinician with lived experience of SCI.

Inclusion Criteria

Participants are eligible to be included in the trial only if all the following criteria apply:

Have sustained an acquired spinal cord injury a minimum of 4 months prior to consent and have completed their primary rehabilitation;
Have a stable neurological level and functional ability of more than two months in duration;
Are over 18 years and able to give informed consent;
Are AIS A, B or low functioning C (more than 75% of key muscles have a power grade <3) as per the International Standards for Neurological Classification of spinal cord injury, and documented by an ISNCSCI/ASIA exam performed by a qualified practitioner within the last six months;
Have a thoracic injury or lower cervical (C5-C8) injury;
Are able and willing to attend an exercise program five times per week for the duration of the priming rehabilitation program, with allowance for two weeks recreational leave;
Are able and willing to attend an exercise program five times per week for at least 12 weeks of the regenerative rehabilitation program and then at least three days per week for the remaining 20 weeks, with allowance for four weeks recreational leave;
Are considered by their general practitioner or specialist medical consultant to be fit to receive the cell transplantation and undertake the exercise program (documented approval by general practitioner required).

Exclusion Criteria

Participants are excluded from the trial if any of the following criteria apply:

Have a high cervical (C1-C4) injury (excluded due to respiratory risk);
Have significant concomitant central nervous system, peripheral nervous system or musculoskeletal system injuries or disorders limiting their ability to exercise;
Have had recent major trauma or surgery within the last 4 months;
Have an existing stage 3 or 4 pressure ulcer according to the National Pressure Ulcer Advisory Panel classification;
Have endocrinopathy or metabolic disorders of the bone that lead to increased risk of injury from the intense long-term exercise therapy, including but not limited to pathological fractures, Paget's disease, lytic or renal bone disease, and senile osteoporosis;
Have a medical history of exposure to medication(s) known to adversely affect mineral or bone metabolism;
Have significant impairment or disability, including physical, neurological or psychological impairments, in addition to the spinal cord injury;
Have a history of long bone fracture incompletely healed;
Have extensive fixed contractures in the upper or lower limbs;
Have severe spasticity that interferes with ability to exercise;
Have uncontrolled neuropathic pain;
Have autonomic dysreflexia without a management plan;
Have a known allergic sensitivity to antibiotics used in the nerve bridge production process;
Do not have adequate transport options to attend the rehabilitation sessions or the assessments;
Are unable to attend the pre-intervention assessments and the follow-up assessments;
Have any contraindications to FES, MRI, X-ray and other study procedures, such as a cardiac pacemaker, epilepsy, lower limb fracture or pregnancy;
Have any other serious medical condition including but not limited to malignancies, auto-immune disorders (requiring continuous pharmaceutical management), psychiatric, behavioural or drug dependency problems, which are likely to influence the participant's ability to cooperate or, in the opinion of the trial investigator, would prevent adherence to the protocol;
Have symptomatic, radiologically demonstrated, or provocatively demonstrated ischaemic heart disease;
Have current thromboembolic disease;
Are using illicit drugs;
Are participating in other clinical trials (including medication, therapeutic interventions and alternative therapies).
Are unable to tolerate expected exercise load.
Are unable to comply with the assessment regime (such as having claustrophobia which prevents MRI procedures being conducted);
Are unable to demonstrate that they have adequate social/family/carer support at home to enable their participation throughout the trial.
Evidence of an active infection, confirmed by testing, of a type that would pose an unacceptable risk for the viability of the nasal biopsy, the cell production, or the nerve bridge production.

ID	Term
D013118	Spinal Cord Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D020196	Trauma, Nervous System

ID	Term
D000359	Aftercare
D003266	Continuity of Patient Care
D005791	Patient Care
D013812	Therapeutics