Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000145707
Ethics application status
Approved
Date submitted
17/01/2022
Date registered
28/01/2022
Date last updated
15/04/2024
Date data sharing statement initially provided
28/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Driving functional recovery after spinal cord injury using transcutaneous electrical spinal cord neuromodulation (TESCoN)
Scientific title
Efficacy and safety of transcutaneous electrical spinal cord neuromodulation (TESCoN) after spinal cord injury
Secondary ID [1] 306228 0
Nil
Universal Trial Number (UTN)
U1111-1273-3194
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Spinal cord injury 324949 0
Condition category
Condition code
Neurological 322378 322378 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Upper limb rehabilitation will be provided in combination with transcutaneous spinal cord neuromodulation (TESCoN), for at least 2 hours per day, 5 days per week for 4 weeks.
The rehabilitation will be provided by a physiotherapist experienced in the management of SCI and will be tailored to the motor capacity of each participant. It may include:
- strengthening exercises (e.g. resisted movements using weights or manual resistance as in proprioceptive neuromuscular facilitation patterns)
- assisted and/or resisted movements aimed at facilitating and strengthening voluntary trunk muscle activity in lying (supine. prone, side-lying) or sitting. Practice of functional tasks that involve movement over and outside of the base of support will also be included.
- intensive training of gross and fine motor skill tasks (e.g. reaching for and manipulating objects of different size, weight and texture)
- playing computer games that encourage hand movements
TESCoN, provided concurrently with upper limb rehabilitation will be delivered via electrodes placed midline between the spinous processes of the C3-C4 and C6-C7 vertebrae using a stimulator (SpineX Inc, Ca, USA). Biphasic rectangular 1ms impulses will be applied, with a frequency of 30Hz, filled with a carrier frequency of 10Hz. This stimulation permits currents of up to 80-120 mA to be delivered to the skin without discomfort. Stimulation will be introduced gradually and adjusted according to participant comfort. TESCoN will be delivered throughout the rehabilitation sessions, but may be turned off for short periods to assess the participant's ability to perform voluntary movements.
Adherence to the intervention will be monitored through daily attendance records.
Intervention code [1] 322631 0
Treatment: Devices
Intervention code [2] 322632 0
Rehabilitation
Comparator / control treatment
No control group or similar
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330146 0
Combined efficacy and safety outcome.
Efficacy: a change equal to or more than the predefined outcome-specific change on at least one of four priority outcomes: Manual Muscle Strength Test (MMTS), Prehension, Trunk function (sitting balance), or the self-care section of the Spinal Cord Independence Measure (SCIM).
- a change equal to or more than 5 points on MMTS of the GRASSP for AIS A/B or 8 points for AIS C/D where there is bilateral involvement, or 5 points for unilateral involvement
OR
- a change of 2 points on the Prehension Performance Test of the GRASSP for AIS A/B or 4 points for AIS C/D
OR
- a change in Trunk Function (sitting balance): maximum balance range in sitting measured using a sway meter. Postural sway and movements to test the limits of stability will also be recorded by inertial sensors placed on the sternum and sacrum.
OR
- a change of 4 points for AIS A/B and 6 points for AIS C/D on the self-care section of the SCIM
AND
- No deterioration between baseline and post-intervention assessments on any of the priority outcomes listed

Safety: no incidence of autonomic dysreflexia, or an increase in pain or spasticity associated with TESCoN
Timepoint [1] 330146 0
One or more of: Manual Muscle Strength Test (MMTS), Prehension, Trunk function (sitting balance),, the self-care section of the Spinal Cord Independence Measure (SCIM) - baseline and post-intervention. Safety assessed continuously throughout all sessions
Secondary outcome [1] 405050 0
Hand function measured by the Graded Refined Assessment of Strength, Sensation, and prehension (GRASSP)
Timepoint [1] 405050 0
Post-intervention and 3-months post intervention
Secondary outcome [2] 405051 0
Grip and pinch strength measured using Jamar dynamometers
Timepoint [2] 405051 0
Post-intervention and 3-months post-intervention
Secondary outcome [3] 405052 0
Performance in activities of daily living and mobility measured using Spinal Cord Independence Measure III (SCIM III)
Timepoint [3] 405052 0
Post-intervention and 3-months post-intervention
Secondary outcome [4] 405053 0
Autonomic function measured using the International Standards to document remaining Autonomic Function after SCI (ISAFSCI)
Timepoint [4] 405053 0
Post-intervention and 3-months post-intervention
Secondary outcome [5] 405054 0
Self-reported bladder function using the Neurogenic Bladder Symptom Score
Timepoint [5] 405054 0
Post-intervention and 3 months post-intervention
Secondary outcome [6] 405055 0
Self-reported bowel function using the Neurogenic Bowel Dysfunction Score
Timepoint [6] 405055 0
Post-intervention and 3 months post-intervention
Secondary outcome [7] 405056 0
24-hour blood pressure monitoring will be performed using a Card(X)plore monitor (Meditech, Budapest Hungary) with an appropriately sized cuff, worn by participants for a 24-hour period. This will be applied by the project assessor at the time of the assessment visits and removed by participants the next day. Measurements will be taken half-hourly during the day (0600–2200 hours) and hourly at night (2200–0600 hours) and analysed according to mean day (1000-2000 hours) and night (0000-0600 hours) values for systolic and diastolic BP.
Timepoint [7] 405056 0
Pre-intervention and immediately post-intervention
Secondary outcome [8] 405057 0
3-day urinary output measurement will involve recording the time that participants void or empty their catheter bag on waking on the first day (Day 1) and then recording urine volumes and times at each void or each time the catheter bag is emptied, until and including the measurement on first waking on Day 4. A measuring jug will be provided for measurement of voided urine or urine emptied from the catheter bag. Day and night rates or urine output will be calculated to determine whether the whether the rate of urine output at night was significantly different from the rate during the day.
Timepoint [8] 405057 0
Pre-intervention and immediately post-intervention
Secondary outcome [9] 434027 0
Threshold tracking to assess peripheral nerve function
Timepoint [9] 434027 0
Secondary outcome [10] 434028 0
Threshold tracking to assess peripheral nerve function
Timepoint [10] 434028 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up

Eligibility
Key inclusion criteria
1. Confirmed motor complete (AIS grade A or B), or incomplete (AIS grade C or D) tetraplegia at the time of enrolment in the study with injury below C4 vertebral level
2. Subacute (2-6 months post-SCI), or chronic (12 months or more post-SCI)
3. Aged between 15 and 75 years
4. Have medical clearance to participate
5. Able to comply with attendance requirements for the study
Minimum age
15 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Other neurological disorders: significant head injury, brachial plexus, or peripheral nerve injury
2. Previous upper limb reconstructive surgery
3. Pre-existing conditions: diabetes, elevated blood pressure
4. Severe cognitive impairment that precludes consent or ability to follow instructions
5. Skeletal or joint injury significantly limiting range of movement of upper limbs
6. Contraindications to stimulation (pacemaker, pregnancy, breast feeding, cancer).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Flexible adaptive Bayesian optimal phase IIa (BOP2) basket design, with 4 strata of participants to be recruited:
1. Subacute spinal cord injury (SCI) with motor complete (AIS grade A or B) tetraplegia
2. Subacute SCI with incomplete (AIS grade C or D) tetraplegia
3. Chronic SCI with motor complete (AIS grade A or B) tetraplegia
4. Chronic SCI with incomplete (AIS grade C or D) tetraplegia
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The sample size for each individual stratum has been calculated using the BOP2 Program (PID: 960; Version: V1.3.17.0). Optimal stopping boundaries have been pre-specified and the criteria for the combined efficacy/safety primary outcome determined on the basis of published data. The design allows the study to satisfy conventional frequentist power constraints, i.e., to yield power of 0.8 using false positive threshold of 0.05, with 20 participants (cohort size of 5) per stratum.

Individual interventions will be analysed in accordance with pre-specified rules to be declared promising or otherwise. Observed proportions of participants with positive primary outcome (composite of efficacy and lack of safety concerns) in each stratum will be reported, together with respective 95% confidence intervals. Longitudinal analyses of individual secondary and exploratory outcomes collected to inform the design of subsequent Phase IIb/III trials will be investigated using mixed effect regression modelling with individual participants treated as random effects.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/06/2022
Actual
18/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26402 0
Royal Talbot Rehabilitation Centre - Kew
Recruitment postcode(s) [1] 42378 0
3101 - Kew

Funding & Sponsors
Funding source category [1] 310574 0
Government body
Name [1] 310574 0
Australian Government Department of Health (Medical Research Future Fund)
Country [1] 310574 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Grattan Street Parkville, Victoria 3010
Country
Australia
Secondary sponsor category [1] 311756 0
None
Name [1] 311756 0
Address [1] 311756 0
Country [1] 311756 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310182 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 310182 0
145 Studley Road, Heidelberg Vic 3084
Ethics committee country [1] 310182 0
Australia
Date submitted for ethics approval [1] 310182 0
16/02/2022
Approval date [1] 310182 0
27/04/2022
Ethics approval number [1] 310182 0

Summary
Brief summary
This project addresses a significant unmet need: recovery of arm and hand function in people with tetraplegia (loss of use of the arms and legs). This issue is ranked by survivors as being of the highest importance, more important than the ability to walk. A novel non-invasive method of spinal cord stimulation (transcutaneous spinal cord neuromodulation – TESCoN) will be trialled for the first time in Australia, and in both subacute and chronic tetraplegia. Electrodes on the skin at the back of the neck will deliver a unique form of stimulation to the spinal cord without causing discomfort. This will modulate (alter the activity of) spared but non-functional pathways as well as the spinal circuitry below the injury level. When combined with intensive rehabilitation of the arm and hand, TESCoN leads to altered connections within the spinal cord, resulting in improved function. TESCoN enhances the effect of intensive rehabilitation and is not a replacement for it. This study will be an open-label trial using an adaptive design, with a combined efficacy and safety endpoint and clear rules for stopping the trial if the intervention is shown to be ineffective and/or unsafe. TESCoN is expected to lead to improvements in function that are superior to those obtained with current best practice rehabilitation. Such recovery of function may have a substantial impact on independence, potential for employment, and quality of life..
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116778 0
Prof Mary Galea
Address 116778 0
Department of Medicine, The University of Melbourne
4th Floor, Clinical Sciences Building
Royal Melbourne Hospital
Parkville Vic 3050
Country 116778 0
Australia
Phone 116778 0
+61 418173521
Fax 116778 0
Email 116778 0
m.galea@unimelb.edu.au
Contact person for public queries
Name 116779 0
Prof Mary Galea
Address 116779 0
Department of Medicine, The University of Melbourne
4th Floor, Clinical Sciences Building
Royal Melbourne Hospital
Parkville Vic 3050
Country 116779 0
Australia
Phone 116779 0
+61 418173521
Fax 116779 0
Email 116779 0
m.galea@unimelb.edu.au
Contact person for scientific queries
Name 116780 0
Prof Mary Galea
Address 116780 0
Department of Medicine, The University of Melbourne
4th Floor, Clinical Sciences Building
Royal Melbourne Hospital
Parkville Vic 3050
Country 116780 0
Australia
Phone 116780 0
+61 418173521
Fax 116780 0
Email 116780 0
m.galea@unimelb.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 underlying published results only
When will data be available (start and end dates)?
Immediately following publication. Data will be available for 5 years after publication.
Available to whom?
On a case by case basis at the discretion of the primary Sponsor.
Available for what types of analyses?
Only for IPD meta-analyses
How or where can data be obtained?
Access through Principal Investigator, Prof Mary Galea (m.galea@unimelb.edu.au)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.