Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000391572
Ethics application status
Approved
Date submitted
15/01/2024
Date registered
3/04/2024
Date last updated
3/04/2024
Date data sharing statement initially provided
3/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety, Feasibility, Efficacy of Olfactory cell transplantation therapy combined with intensive exercise rehabilitation to repair chronic traumatic spinal cord injury.
Scientific title
Safety, Feasibility, Efficacy of Olfactory cell transplantation therapy combined with intensive exercise rehabilitation to repair chronic spinal cord injury in participants with traumatic spinal cord injury.
Secondary ID [1] 311326 0
GUSIP03
Universal Trial Number (UTN)
Trial acronym
Griffith University Spinal Injury Project 03 (GUSIP03)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal Cord Injury 332578 0
Condition category
Condition code
Neurological 329276 329276 0 0
Other neurological disorders
Physical Medicine / Rehabilitation 329277 329277 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomised, blinded and controlled Phase I/IIa 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 of 1-2 cm in length 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 and go for 12 weeks, then surgery and cell transplantation will occur at week 13 followed by 3-4 weeks of recovery, and then rehabilitation for 32 (weeks 17-48).
Intervention code [1] 327768 0
Treatment: Other
Intervention code [2] 327769 0
Treatment: Surgery
Intervention code [3] 328012 0
Rehabilitation
Comparator / control treatment
The control group will receive the same high-intensity rehabilitation program as the intervention group. The control group will not receive the olfactory cell nerve bridge transplant.
Control group
Active

Outcomes
Primary outcome [1] 337095 0
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.
Timepoint [1] 337095 0
2 weeks after completion of full intervention (week 48) at week 50
Primary outcome [2] 337096 0
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.
Timepoint [2] 337096 0
Assessed 2 weeks after completion of full intervention (week 48) at week 50.
Primary outcome [3] 337097 0
Efficacy
Timepoint [3] 337097 0
CT/MRI/FA-DTI and fMRI measured at screening (before intervention), Week 12 of priming rehabilitation program, Week 17 (post cell transplant surgery and recovery/beginning of regenerative rehabilitation program and again at week 25, week 37 and week 48 post-commencement of intervention.
Secondary outcome [1] 430682 0
Changes in the neurological classification of SCI and sensory function:
Timepoint [1] 430682 0
Outcome measured at screening, then week 12, week 17, week 29, 41 and week 48 post-commencement of intervention
Secondary outcome [2] 430683 0
Changes in electrophysiological assessments - somatosensory evoked potentials (SSEP)
Timepoint [2] 430683 0
Outcome measured at screening, then after intervention commencement at week 12, week 13 (SSEP during transplantation surgery), week 17, week 50 (post-rehab follow up).
Secondary outcome [3] 430684 0
Changes in biomarkers (CSF): Thousands of protein biomarkers will be assessed from the one sample. Examples of biomarkers of interest include markers for inflammation and neural injury.
Timepoint [3] 430684 0
Outcome measured at screening, then week 16 and week 18 post-commencement of intervention.
Secondary outcome [4] 430685 0
Changes in biomarkers (Serum). Thousands of protein biomarkers will be assessed from the one sample. Examples of biomarkers of interest include markers for inflammation and neural injury.
Timepoint [4] 430685 0
Outcome measured at screening, then week 12, week 15, week 17, week 33, week 48 post-commencement of intervention.
Secondary outcome [5] 430689 0
Changes in vital signs (Body temperature, blood pressure, heart rate, respiratory rate, oxygen saturation, electrical activity of the heart). All vital signs will be assessed as a composite secondary outcome.
Timepoint [5] 430689 0
Outcome measured at screening, then week 1, week 7, week 12, week 17 and week 48 (post-intervention commencement). ECG monitoring will be done on week 12 as a pre-operative check up.
Secondary outcome [6] 430690 0
pulmonary function (FEV1, FVC and FEV1/FVC ratio)
Timepoint [6] 430690 0
Outcome measured at screening, week 1, week 7, week 12, week 17, week 29, week 48 post-commencement of intervention
Secondary outcome [7] 430691 0
Bone Mineral Density
Timepoint [7] 430691 0
Outcome measured at screening, then week 12, week 17, week 29, week 48 post-commencement of intervention
Secondary outcome [8] 430692 0
Blood and serum tests: Full Blood Count Testing
Timepoint [8] 430692 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [9] 430694 0
Changes in motor function
Timepoint [9] 430694 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [10] 430695 0
Changes in strength
Timepoint [10] 430695 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [11] 430696 0
Changes in pain
Timepoint [11] 430696 0
Outcome measured at Screening, week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention
Secondary outcome [12] 430697 0
Changes in cardiovascular function
Timepoint [12] 430697 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [13] 430698 0
Changes in bowel, bladder function and independence
Timepoint [13] 430698 0
Outcome measured at Screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention
Secondary outcome [14] 430699 0
Changes in fatigue
Timepoint [14] 430699 0
Outcome measured at Screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention, week 50 (post-rehab follow up),
Secondary outcome [15] 430700 0
Changes in Depression, Anxiety and Stress. All measures tested together as part of DASS-21 scale (Depression, Anxiety and Stress Scale - 21 Items.
Timepoint [15] 430700 0
Outcome measured at Screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention, week 50 (post-rehab follow up)
Secondary outcome [16] 430701 0
Changes in Quality of Life
Timepoint [16] 430701 0
Outcome measured at Screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention, week 50 (post-rehab follow up)
Secondary outcome [17] 430703 0
Quantify the severity of suicidal ideation and behavior.
Timepoint [17] 430703 0
Outcome measured at Screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention.
Secondary outcome [18] 430704 0
Measure of muscle tone
Timepoint [18] 430704 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48 post commencement of intervention
Secondary outcome [19] 430705 0
Changes in lived experience
Timepoint [19] 430705 0
Outcome measured at week 1, week 12, week 17, week 50 post commencement of intervention.
Secondary outcome [20] 431816 0
Additional Primary Outcome (4): Feasibility of Surgical transplantation of nerve bridges.
Timepoint [20] 431816 0
2 weeks after completion of full intervention (week 48) at week 50
Secondary outcome [21] 431817 0
Additional Primary Outcome (5): Feasibility of delivery of rehabilitation and assessments.
Timepoint [21] 431817 0
2 weeks after completion of full intervention (week 48) at week 50
Secondary outcome [22] 433023 0
Changes in electrophysiological assessments - Motor Evoked Potentials (MEP)
Timepoint [22] 433023 0
Outcome measured at screening, then after intervention commencement at week 12, week 13 (MEP during transplantation surgery), week 17, week 50 (post-rehab follow up).
Secondary outcome [23] 433066 0
Blood and serum tests: Coagulation studies
Timepoint [23] 433066 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [24] 433067 0
Blood and serum tests: Blood Sugar Tests
Timepoint [24] 433067 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [25] 433068 0
Blood and serum tests: Serological tests
Timepoint [25] 433068 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [26] 433069 0
Blood and serum tests: Liver function tests
Timepoint [26] 433069 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [27] 433070 0
Blood and serum tests: Lipid profile
Timepoint [27] 433070 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [28] 433071 0
Blood and serum tests: Brain natriuretic peptide (BNP)
Timepoint [28] 433071 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.
Secondary outcome [29] 433074 0
Blood and serum tests: Chem20 panel
Timepoint [29] 433074 0
Outcome measured at screening, then week 1, week 7, week 12, week 17, week 29, week 41, week 48, post commencement of intervention.

Eligibility
Key inclusion 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 study only if all the following criteria apply:
1. Have sustained a traumatic spinal cord injury a minimum of 4 months prior to consent and have completed their primary rehabilitation;
2. Have a stable neurological level and functional ability of more than two months in duration;
3. Are over 18 years and able to give informed consent;
4. 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;
5. Have a thoracic injury or lower cervical (C5-C8) injury;
6. 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;
7. 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;
8. See public notes section.
9. 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).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
1. Have a high cervical (C1-C4) injury (excluded due to respiratory risk);
2. Have significant concomitant central nervous system, peripheral nervous system or musculoskeletal system injuries or disorders limiting their ability to exercise;
3. Have had recent major trauma or surgery within the last 4 months;
4. Have an existing stage 3 or 4 pressure ulcer according to the National Pressure Ulcer Advisory Panel classification;
5. Have endocrinopathy or metabolic disorders of the bone, including but not limited to Paget’s disease, lytic or renal bone disease, and senile osteoporosis;
6. Have a medical history of exposure to medication(s) known to affect mineral or bone metabolism;
7. Have significant impairment or disability, including physical, neurological or psychological impairments, in addition to the spinal cord injury;
8. Have a history of long bone fracture incompletely healed;
9. Have extensive fixed contractures in the upper or lower limbs;
10. Have severe spasticity;
11. Have uncontrolled neuropathic pain;
12. Have autonomic dysreflexia without a management plan;
13. Do not have adequate transport options to attend the rehabilitation sessions;
14. Are unable to attend the pre-intervention assessments and the follow-up assessments;
15. Are unable to attend the surgery at GCUH (if in cell+rehabilitation group);
16. Have any contraindications to FES such as a cardiac pacemaker, epilepsy, lower limb fracture or pregnancy;
17. 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 study investigator, would prevent adherence to the protocol;
18. Have symptomatic, radiologically demonstrated, or provocatively demonstrated ischaemic heart disease;
19. Have current thromboembolic disease;
20. Are using illicit drugs;
21. Are participating in other clinical trials (including medication, therapeutic interventions and alternative therapies) or taking medications (including herbal preparations) that are not considered to be standard care as per the protocol;
22. Are unable to tolerate expected exercise load.
23. Are unable to comply with the assessment regime (such as having claustrophobia which prevents MRI procedures being conducted);
24. See public notes section.
25. Are unable to demonstrate that they have adequate social/family/carer support at home to enable their participation throughout the trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified allocation will be employed as we will be enrolling people over time, so it will be stratified (ASIA A, B, C, time since injury, para, quad) and matched (as best we can). Allotment of participants into the two groups will be randomised (using a randomisation table created by computer). For example, we will enrol 3 people within the stratification that we are after, and of those three they will then be randomly assigned two to treatment, one to control.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical Hypotheses
The study will assess feasibility, safety and efficacy of treating chronic spinal cord injury with a combined approach of olfactory cell nerve bridge engraftment and intensive rehabilitation.
There are no hypotheses tested regarding the amount of change in vital signs, motor function, strength, cardiovascular function, sensory function, and psychosocial health that will potentially be observed due to the nature of the study and the limited sample size.


For the purposes of analysis, the following analysis sets are defined:
Full analysis set: • All participants enrolled in the study will be included in the analyses.
Safety analysis set: • All participants who are exposed to the study intervention will be included in the analyses.

Primary Endpoint(s)/Estimand(s) Analysis
Descriptive statistics will be presented using frequencies and percentages for categorical data as well as qualitative analysis to report on open-ended questions.
Acceptability of the program will be assessed by calculating retention rate and participant compliance at the end of the rehabilitation programs (week 12 of priming rehabilitation and final week of regenerative rehabilitation). Overall retention rate for the rehabilitation only and cell+rehabilitation groups will correspond to the total number of participants who stayed for the whole program divided by the total number of participants recruited for the program and multiplied by 100

Secondary Endpoint(s) Analysis
Descriptive statistics will be presented at different timepoints (where available):
These statistics will use median, inter-quartile range, and range for continuous data. Frequencies and percentages will be presented for categorical data.
The change scores between baseline and each timepoint as well as percentage change scores (calculated as the difference between timepoints and divided by baseline value and multiplied by 100) will be calculated and reported using descriptive statistics. Change scores will also be dichotomised to evaluate how many participants increased, decreased, or stayed stable during the program, from the start to the end, for associated measures described above.

Sample Size Determination
With the aim of obtaining indications of efficacy and responders versus non-responders, thirty participants of any gender aged 18 years or over will be included in the study. 20 will be allocated to the treatment group of cell+rehabilitation and 10 to the control rehabilitation only group. Inclusion of a control group for the study has been endorsed by the Consumer Research Panel.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2024
Actual
Date of last participant enrolment
Anticipated
15/08/2024
Actual
Date of last data collection
Anticipated
1/08/2028
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 26026 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 41872 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 315579 0
Charities/Societies/Foundations
Name [1] 315579 0
Perry Cross Spinal Research Foundation
Country [1] 315579 0
Australia
Funding source category [2] 315584 0
Charities/Societies/Foundations
Name [2] 315584 0
Clem Jones Foundation
Country [2] 315584 0
Australia
Funding source category [3] 315866 0
University
Name [3] 315866 0
Griffith University
Country [3] 315866 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
170 Kessels Road, Nathan, 4111, Queensland
Country
Australia
Secondary sponsor category [1] 317680 0
None
Name [1] 317680 0
Address [1] 317680 0
Country [1] 317680 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314475 0
Gold Coast Hospital and Health Service HREC
Ethics committee address [1] 314475 0
Office for Research Governance and Development Level 2 Block E – Pathology and Education 1 Hospital Boulevard Southport, QLD, 4215
Ethics committee country [1] 314475 0
Australia
Date submitted for ethics approval [1] 314475 0
17/01/2024
Approval date [1] 314475 0
20/03/2024
Ethics approval number [1] 314475 0
HREC/2024/QGC/105231

Summary
Brief summary
This is a randomised, blinded and controlled Phase I/IIa 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.
Trial website
Trial related presentations / publications
Public notes
Please note inclusion criteria #8: Are vaccinated against COVID-19 and have had their COVID-19 booster (if eligible); and exclusion criteria #24: Are not vaccinated against COVID-19 and have not had their COVID-19 booster (if eligible).

Contacts
Principal investigator
Name 131714 0
Dr Brent McMonagle
Address 131714 0
Gold Coast University Hospital, 1 Hospital Blvd, Southport QLD 4215
Country 131714 0
Australia
Phone 131714 0
+61 7 55392399
Fax 131714 0
Email 131714 0
brent@drbrentmcmonagle.com.au
Contact person for public queries
Name 131715 0
Dr Andrew Rayfield
Address 131715 0
Menzies Health Institute Queensland Ian O'Connor Building (G40) Room 9.61 Gold Coast Campus, Parklands Drive, Griffith University, Southport, QLD, 4222
Country 131715 0
Australia
Phone 131715 0
+61 756780917
Fax 131715 0
Email 131715 0
a.rayfield@griffith.edu.au
Contact person for scientific queries
Name 131716 0
Dr Andrew Rayfield
Address 131716 0
Menzies Health Institute Queensland Ian O'Connor Building (G40) Room 9.61 Gold Coast Campus, Parklands Drive, Griffith University, Southport, QLD, 4222
Country 131716 0
Australia
Phone 131716 0
+61 756780917
Fax 131716 0
Email 131716 0
a.rayfield@griffith.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie published results, after deidentification (text, tables, figures, and appendices).
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following article publication
Available to whom?
Researchers who provide a methodologically sound proposal.
Available for what types of analyses?
To achieve aims in the approved proposal.
How or where can data be obtained?
Proposals should be directed to j.stjohn@griffith.edu.au . To gain access, data requestors will need to sign a data access agreement.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21399Study protocol  j.stjohn@griffith.edu.au
21400Statistical analysis plan  j.stjohn@griffith.edu.au
21401Analytic code  j.stjohn@griffith.edu.au



Results publications and other study-related documents

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