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Trial registered on ANZCTR


Registration number
ACTRN12618001770257
Ethics application status
Approved
Date submitted
23/10/2018
Date registered
29/10/2018
Date last updated
2/03/2022
Date data sharing statement initially provided
29/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Reversing peripheral nerve dysfunction after spinal cord injury
Scientific title
Reversing peripheral nerve dysfunction using functional electrical stimulation after spinal cord injury
Secondary ID [1] 296425 0
None
Universal Trial Number (UTN)
U1111-1222-6740
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
spinal cord injury 310150 0
Condition category
Condition code
Neurological 308901 308901 0 0
Other neurological disorders
Injuries and Accidents 308924 308924 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Functional electrical stimulation will be delivered using the ReGrasp device. Surface electrodes are embedded in a cuff worn on the forearm. The stimulator can be operated independently by simple head motions detected by an earpiece containing an accelerometer. The earpiece sends radio frequency signals to the stimulator, advancing it through a 3-state sequence: hand opening, grasp, no stimulation. Typical pulse parameters are: biphasic rectangular wave pulses, frequency 20 to 30 pulses/sec, pulse duration 100 to 200 microseconds, amplitude 25 to 35mA, However, clinicians will be able to adjust values for patient comfort. Participants and their carers will be trained in the use of the ReGrasp, and participants will be asked to use the device for at least one hour daily, 5 days per week for 6 weeks prior to nerve transfer surgery. They will be asked to record their daily use of the ReGrasp in a diary, and adherence will be monitored through weekly phone calls by the therapist to participants, who will also monitor any adverse events. Surgery will occur between 1 and 2 weeks after cessation of the stimulation. This surgery does not form part of the intervention.
Intervention code [1] 312729 0
Treatment: Devices
Comparator / control treatment
Historical histological data collected in 15 participants with spinal cord injury who underwent nerve transfer surgery between 2013 and 2015. These participants did not have functional electrical stimulation prior to surgery.
Control group
Historical

Outcomes
Primary outcome [1] 307868 0
Axon/nerve fibre ratio, measured in sections of nerve specimens embedded in Araldite Epon, and stained with Methylene Blue. Sections will be analysed using an Olympus BX60 microscope and x100 oil immersion objective, interfaced with monitor and image analysis software,
Timepoint [1] 307868 0
At time of surgery
Secondary outcome [1] 353180 0
Presence or absence of fibrillations on needle electromyography (EMG) pre-operatively
Timepoint [1] 353180 0
Prior to surgery
Secondary outcome [2] 407071 0
Grip and pinch strength, assessed using grip and pinch dynamometers
Timepoint [2] 407071 0
Baseline, post FES intervention, 12- and 24 months post-surgery
Secondary outcome [3] 407072 0
Action Research Arm Test (ARAT)
Timepoint [3] 407072 0
Baseline, post-FES intervention, 12- and 24 months post surgery
Secondary outcome [4] 407073 0
Grasp-Release Test (GRT)
Timepoint [4] 407073 0
Baseline, post-FES intervention, 12- and 24 months post-surgery
Secondary outcome [5] 407074 0
Canadian Occupational Performance Measure (COPM) will measure a participant's perception of their performance and satisfaction.
Timepoint [5] 407074 0
Baseline, post-FES intervention, 12- and 24 months post surgery
Secondary outcome [6] 407075 0
Daily function assessed by the Spinal Cord Independence Measure (SCIM).
Timepoint [6] 407075 0
Baseline, post-FES intervention, 12- and 24 months post surgery
Secondary outcome [7] 407076 0
Spinal Cord Injury version of the Multidimensional Pain Inventory
Timepoint [7] 407076 0
Baseline, post-FES intervention, 12- and 24 monts post-surgery
Secondary outcome [8] 407077 0
Personal Wellbeing Index
Timepoint [8] 407077 0
Baseline, post-FES intervention, 12- and 24 months post-surgery
Secondary outcome [9] 407078 0
Health Utilities Index, Mark 3 (HUI-3) will be used to measure health status and to conduct a cost-utility analysis..
Timepoint [9] 407078 0
Baseline, post-FES intervention, 12- and 24 months post-surgery
Secondary outcome [10] 407079 0
Assessment of Quality of Life-4D (AQoL-4)
Timepoint [10] 407079 0
Baseline, post-FES intervention, 12- and 24 months post-surgery

Eligibility
Key inclusion criteria
1. Complete or incomplete tetraplegia with C5 – C7 motor neurological level
2. Assessed as suitable for nerve transfer surgery by the surgical and occupational therapy team at the Upper Limb Program Multidisciplinary Clinic at Austin Health
3. Consent to nerve transfer surgery and intra-operative nerve and muscle biopsies after being fully informed about expected outcomes, potential risks, surgical procedure, recovery time, postoperative therapy commitments.
4. Able to comply with therapy protocols pre-operatively
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Accompanying head injury, brachial plexus or peripheral nerve injury at the time of, or preceding the spinal cord injury
2. Any other pre-existing neurological condition
3. Cognitive impairment limiting ability to consent to surgery or comply with postoperative rehabilitation
4. Skeletal or joint injury signifcantly limiting passive range of movement across a joint relevant to the proposed nerve transfer
5. Contraindications to functional electrical stimulation

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
No applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
For the primary analysis, the difference in the ratio of axon CSA/nerve fibre CSA in stimulated and non-stimulated nerves will be examined using a t-test if the data are normally distributed, and non-parametric tests if assumptions of normality are not met. Secondary analyses will examine differences on all other histological features between stimulated and non-stimulated nerves and healthy control specimens, including the length of the node of Ranvier, as well as changes in hand function scores before and after the 6 weeks of pre-operative FES, and on changes in quality of life, pain and wellbeing between baseline and 24 months.

Cost-utility analysis: The two treatment groups will be compared in terms of their costs and quality-adjusted life years (QALYs) estimated by HUI-3 to estimate the cost-utility of FES and nerve transfer surgery (NTS) compared to NTS alone. Analysis will be undertaken on an intention-to-treat basis. Between-group cost and QALY differences will be presented as a point estimate incremental cost utility ratio (ICUR) to summarise the estimated additional cost per additional QALY gained from adding the 6-week FES program prior to upper limb NTS compared to NTS alone.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/03/2020
Actual
22/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
15
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12241 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 24427 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 301009 0
University
Name [1] 301009 0
University of Melbourne
Country [1] 301009 0
Australia
Funding source category [2] 301027 0
Hospital
Name [2] 301027 0
Austin Health
Country [2] 301027 0
Australia
Funding source category [3] 310912 0
Charities/Societies/Foundations
Name [3] 310912 0
Wings For Life
Country [3] 310912 0
Austria
Funding source category [4] 310913 0
Government body
Name [4] 310913 0
Transport Accident Commission, Victoria
Country [4] 310913 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
145 Studley Road,
Heidelberg, Victoria, 3084
Country
Australia
Secondary sponsor category [1] 300598 0
None
Name [1] 300598 0
Address [1] 300598 0
Country [1] 300598 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301767 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 301767 0
Austin Health,
145 Studley Road,
Heidelberg, Victoria, 3084
Ethics committee country [1] 301767 0
Australia
Date submitted for ethics approval [1] 301767 0
31/10/2018
Approval date [1] 301767 0
30/07/2019
Ethics approval number [1] 301767 0

Summary
Brief summary
This study will specifically investigate whether functional electrical stimulation (FES) reverses myelin abnormalities in peripheral nerves of people with spinal cord injury. Participants who are scheduled to undergo nerve transfer surgery will be asked to undertake a program of FES using the ReGrasp device (Rehabtronics Inc, Edmonton Canada) for at least one hour dail, 5 days per week for 6 weeks prior to the surgery. This device enables a person to close and open the hand and can be operated independently by simple head motions detected by an earpiece. Biopsies of the relevant nerves and muscles will be obtained during the surgery, and these will be processed, analysed and compared with those obtained from previous nerve transfer surgery participants (historical controls). The primary outcome measure is the axon/nerve fibre ratio. Secondary outcomes include clinical assessments of hand function, independence, pain, well-being and quality of life, with participants being followed up for 24 months post-surgery. A cost-utility analysis will also be conducted.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88030 0
Prof Mary Galea
Address 88030 0
Department of Medicine (Royal Melbourne Hospital)
The University of Melbourne
Level 4, Clinical Sciences Building
Royal Melbourne Hospital
Royal Parade
Parkville, Victoria 3052
Country 88030 0
Australia
Phone 88030 0
+61418173521
Fax 88030 0
Email 88030 0
[email protected]
Contact person for public queries
Name 88031 0
Mary Galea
Address 88031 0
Department of Medicine (Royal Melbourne Hospital)
The University of Melbourne
Level 4, Clinical Sciences Building
Royal Melbourne Hospital
Royal Parade
Parkville, Victoria 3052
Country 88031 0
Australia
Phone 88031 0
+61418173521
Fax 88031 0
Email 88031 0
[email protected]
Contact person for scientific queries
Name 88032 0
Mary Galea
Address 88032 0
Department of Medicine (Royal Melbourne Hospital)
The University of Melbourne
Level 4, Clinical Sciences Building
Royal Melbourne Hospital
Royal Parade
Parkville, Victoria 3052
Country 88032 0
Australia
Phone 88032 0
+61418173521
Fax 88032 0
Email 88032 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
It has not yet been decided whether individual participant data will be made available, since this study involves a very small group of participants.


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.