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Trial registered on ANZCTR


Registration number
ACTRN12624000358549
Ethics application status
Approved
Date submitted
1/03/2024
Date registered
28/03/2024
Date last updated
28/03/2024
Date data sharing statement initially provided
28/03/2024
Date results information initially provided
28/03/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Driving functional recovery after spinal cord injury using transcutaneous electrical spinal cord neuromodulation (TESCoN) – pilot study.
Scientific title
Efficacy and safety of transcutaneous electrical spinal cord neuromodulation (TESCoN) after spinal cord injury - a pilot study.
Secondary ID [1] 311524 0
Nil
Universal Trial Number (UTN)
U1111-1304-2026
Trial acronym
Linked study record
This study was a pilot study related to registration record ACTRN12622000145707. We commenced that study and collected data for 5 participants before it became clear that further refinement of the primary outcome measure was required and an ethics amendment was submitted for this. We therefore decided that these 5 participants would serve as a pilot and would be analysed separately from the participants who were enrolled after the ethics amendment.

Health condition
Health condition(s) or problem(s) studied:
Spinal cord injury 332873 0
Condition category
Condition code
Neurological 329593 329593 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 spinal cord injury (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)
- 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 the participant's tolerance. 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] 327979 0
Treatment: Devices
Intervention code [2] 327980 0
Rehabilitation
Comparator / control treatment
No control group or similar
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337376 0
Combined efficacy (at least 10 points improvement on the Manual Muscle Testing Score) and safety (no safety concerns, i.e. no episode of autonomic dysreflexia, or an increase in pain or spasticity associated with TESCoN) outcome:.
Timepoint [1] 337376 0
Manual Muscle Test Score - baseline, and post-completion of 4-week intervention program
Safety assessed continuously throughout all sessions
Secondary outcome [1] 431608 0
Hand function measured by the Graded Refined Assessment of Strength, Sensation, and Prehension instrument.
Timepoint [1] 431608 0
Baseline, post-completion of 4-week intervention program, and at 3-months follow-up
Secondary outcome [2] 431609 0
Grip strength.
Timepoint [2] 431609 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up.
Secondary outcome [3] 431610 0
Performance in activities of daily living and mobility measured using Spinal Cord Independence Measure III (SCIM III) questionnaire (composite outcome - independence).
Timepoint [3] 431610 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up
Secondary outcome [4] 431612 0
Autonomic function measured using the International Standards to document remaining Autonomic Function after SCI (ISAFSCI) checklist.
Timepoint [4] 431612 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up
Secondary outcome [5] 431613 0
Self-reported bladder function on the Neurogenic Bladder Symptom Score
Timepoint [5] 431613 0
Baseline, post-completion of 4-week intervention program, and 3 months follow up
Secondary outcome [6] 431614 0
Self-reported bowel function on the Neurogenic Bowel Dysfunction questionnaire
Timepoint [6] 431614 0
Baseline, post-completion of 4-week intervention program, 3 months follow-up
Secondary outcome [7] 431615 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] 431615 0
Baseline and post-completion of 4-week intervention program.
Secondary outcome [8] 431616 0
3-day urinary output measurement
Timepoint [8] 431616 0
Baseline and post-completion of 4-week intervention program.
Secondary outcome [9] 431632 0
Peripheral nerve excitability
Timepoint [9] 431632 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up
Secondary outcome [10] 431634 0
Gait (for participants who are able to walk).
Timepoint [10] 431634 0
Baseline, post-completion of 4-week intervention program, 3 months follow-up
Secondary outcome [11] 433048 0
Pinch strength
Timepoint [11] 433048 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up
Secondary outcome [12] 433052 0
24-hour heart rate measurements
Timepoint [12] 433052 0
Baseline, and post-completion of 4-week intervention program
Secondary outcome [13] 433056 0
Balance (for participants who can stand and walk)
Timepoint [13] 433056 0
Baseline, post-completion of 4-week intervention program, and 3 months follow-up

Eligibility
Key inclusion criteria
1. Confrmed motor complete (American Spinal Injury Association Impairment Scale [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 (3-6 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: signicant 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 signicantly 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
Open (masking not used)
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
A sample size of 5 participants was enrolled in this pilot study.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
24/10/2022
Date of last participant enrolment
Anticipated
Actual
8/02/2023
Date of last data collection
Anticipated
Actual
30/06/2023
Sample size
Target
5
Accrual to date
Final
5
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 42052 0
3101 - Kew

Funding & Sponsors
Funding source category [1] 315815 0
Government body
Name [1] 315815 0
Australian Government Department of Health (Medical Research Future Fund)
Country [1] 315815 0
Australia
Primary sponsor type
University
Name
The University of Melbourne
Address
Country
Australia
Secondary sponsor category [1] 317960 0
None
Name [1] 317960 0
Address [1] 317960 0
Country [1] 317960 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314673 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 314673 0
https://www.austin.org.au/Office-for-Research/
Ethics committee country [1] 314673 0
Australia
Date submitted for ethics approval [1] 314673 0
16/02/2022
Approval date [1] 314673 0
27/04/2022
Ethics approval number [1] 314673 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 132362 0
Prof Mary Galea
Address 132362 0
Department of Medicine, The University of Melbourne, 4th Floor, Clinical Sciences Building, Royal Melbourne Hospital, Parkville VIC 3050
Country 132362 0
Australia
Phone 132362 0
+61 418173521
Fax 132362 0
Email 132362 0
[email protected]
Contact person for public queries
Name 132363 0
Mary Galea
Address 132363 0
Department of Medicine, The University of Melbourne, 4th Floor, Clinical Sciences Building, Royal Melbourne Hospital, Parkville VIC 3050
Country 132363 0
Australia
Phone 132363 0
+61 418173521
Fax 132363 0
Email 132363 0
[email protected]
Contact person for scientific queries
Name 132364 0
Mary Galea
Address 132364 0
Department of Medicine, The University of Melbourne, 4th Floor, Clinical Sciences Building, Royal Melbourne Hospital, Parkville VIC 3050
Country 132364 0
Australia
Phone 132364 0
+61 418173521
Fax 132364 0
Email 132364 0
[email protected]

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 ([email protected])


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.