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Trial registered on ANZCTR


Registration number
ACTRN12622001272785
Ethics application status
Approved
Date submitted
15/09/2022
Date registered
28/09/2022
Date last updated
28/09/2022
Date data sharing statement initially provided
28/09/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
BioSpine: multimodal rehabilitation for individuals with complete chronic spinal cord injury
Scientific title
BioSpine: effect of multimodal rehabilitation on symptom severity in individuals with complete chronic spinal cord injury
Secondary ID [1] 306386 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
traumatic complete chronic spinal cord injury 326989 0
Condition category
Condition code
Neurological 324177 324177 0 0
Other neurological disorders
Physical Medicine / Rehabilitation 324756 324756 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study Devices
The following devices non-invasive devices will be used as part of the intervention
1. Wearable Wireless dry or wet electrode electroencephalography (EEG) headset (e.g., DSI-7, Wearable Sensing, San Diego, CA, USA; All-in-One Biosensing R&D Bundle, OpenBCI, Brooklyn, NY, USA; Sessantaquattro, OT Bioelettronica, Torino (TO), Italy). This device involves non-invasively recording low voltage biosignals (i.e., electroencephalography) from the surface of a person’s scalp. This device employs electrodes that are not disturbed by hair.
2. Functional electrical stimulation (FES) uses an electric current to externally stimulate muscles to artificially create movement. Surface electrodes consisting of adhesive hypoallergenic patches are applied over the muscle groups of interest. For this intervention, pairs electrodes will be places on the muscles of the legs. The electrodes provide nothing but contact for the device and do not cause superficial or any form of damage to the skin or the skin surface. FES is non-invasive and is used in many applications such as cycling, walking, and bladder control, and it is commonly used in rehabilitation. The RT300 (Restorative Therapies, Baltimore, US) and RehaStim 2 (Hasomed, Magdeburg, Germany) devices will be used for this intervention.
3. Cycling ergometer is a stationary motorised bicycle that provide pedal assistance. For this intervention we are going to use a RT300 (Restorative Therapies, Baltimore, US), THERA-Trainer Tigo (THERA-Trainer, Hochdorf, Germany) or an equivalent device, which is wheelchair compatible and enables participants to cycle without dismounting from their wheelchair.
4. Virtual reality (VR) involves visual and/or audible simulated content often produced by a head mounted device and/or headphones. VR can offer the unique experience of being in an environment that is not possible or accessible, allowing a person to visualise an avatar in a virtual environment. VR will be used to create an engaging and stimulating cycling environment for patients and allow for a more immersive experience than presented in the laboratory. A commercially available VR headset will be used for this intervention (e.g., Oculus Rift, Facebook Technologies, LLC, Exertis, UK) or equivalent.
5. Haptic (i.e., vibration) feedback involves sensors attached to the person’s skin. As people with SCI perceive limited sensation below the level of injury, a haptic sensor will be placed above the level of injury (e.g., shoulders or base of the neck) and it will vibrate based on the amount of force applied to the pedals during cycling. The vibration is low powered and comparable to the vibration of a modern smartphone. A commercial or custom-made device will be used for this intervention.
6. Tilt table or standing frames allow moving the participant to an upright position, in a safe and controlled fashion. Positioning the participant upright contributes to reengaging the vestibular and cardiovascular system. The tilt table will primarily be used during the technology introduction stage, allowing the participant to train motor imagery using the brain-computer interface, VR and haptic feedback systems. To reduce the risk of blood pressure drop and orthostatic collapse during tilt table use, the tilt table angle will be increased incrementally, the participant will wear an abdominal binder, and the participant’s blood pressure monitored.

Dosage
Participants will perform at least 150 minutes per week, distributed over 2 to 3 sessions per week, of progressive neurorehabilitation for 52 weeks. One week prior commencement of therapy, participants will be administered 7.5 mg of buspirone hydrochloride in form of oral tablets, twice a day. Administration will continue throughout the intervention. To monitor adherence, at each in-person neurorehabilitation session, participants will be asked whether they have assumed the buspirone hydrochloride tables during the previous days. Additionally, participants will be requested to return unused tablets at the end of every month.

Intervention
An experienced exercise physiologist or physiotherapist will conduct the intervention. At the beginning of each session, the participant will be instrumented with FES electrodes on the main muscles of the lower limbs. The participant will approach the cycling ergometer in a wheelchair (a wheelchair will be provided if necessary) and secured to the pedal of the ergometer. The participant will be donned with a wireless EEG headset and VR headset.
The participant will perform a passive cycling warmup on the ergometer, for a period of at least 5 minutes, to reduce the occurrence of spasticity. During the passive cycling warmup, the participant will cycle on the ergometer without electrical stimulation and with the lowest motorised torque assistance to achieve stable cycling.
A calibration procedure for the brain-computer interface will be performed. This consists of 5-25 minutes wherein a virtual avatar is displayed while performing cycling movement or no movement, and the participant is asked to think about performing the visualised movement. Following calibration, the training phase will start. This involves the participant thinking about cycling. Because of this thought, the legs of the participant will be electrically stimulated to perform the desired cycling movement. The motorised cycling ergometer will also provide pedal assistance to facilitate the task. The ergometer torque will be monitored to facilitate spasm detection and response. During training the participant will also experience cycling in the VR system. Length of training session will logged to monitor participant adherence.

Parameters of the FES stimulation
FES stimulation electrodes will be positioned on the hamstrings, quadriceps, calves muscle groups and on the tibialis anterior, bilaterally. The electric charge of stimulation (i.e., current and pulse width) will be automatically modulated by a custom FES controller throughout the pedaling cycle in order to stimulate muscles only when mechanically advantageous. The frequency of stimulation will be set to 40Hz, and the maximum amount delivered current will not exceed 80mA.
Intervention code [1] 324008 0
Treatment: Devices
Intervention code [2] 324009 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332255 0
Severity of injury, as measured by American Spinal Injury Association (ASIA) Impairment Scale (AIS) assessment
Timepoint [1] 332255 0
Baseline, and at 6 and 12 months from the start of the intervention
Secondary outcome [1] 412727 0
Changes in muscle volume, measured via magnetic resonance imaging (MRI)
Timepoint [1] 412727 0
Baseline, and at 6 and 12 months from the start of the intervention
Secondary outcome [2] 412728 0
Anatomical changes to the spinal cord measured by magnetic resonance imaging (MRI)
Timepoint [2] 412728 0
Baseline, and at 6 and 12 months from the start of the intervention
Secondary outcome [3] 412729 0
Bone density, measured by Dual-energy X-ray absorptiometry (DXA)
Timepoint [3] 412729 0
Baseline and after 12 months from the beginning of the intervention
Secondary outcome [4] 412730 0
Quality of life, as measured by World Health Organisation Quality of Life questionnaire (WHOQOL-BREF)
Timepoint [4] 412730 0
Baseline, and at 3, 6, 9, and 12 months from the start of the intervention.
Secondary outcome [5] 412740 0
Voluntary muscle activation as measured by surface electromyography
Timepoint [5] 412740 0
Baseline and at 3, 6, 9, and 12 months from the start of the intervention
Secondary outcome [6] 412741 0
Somatosensory evoked potentials (SSEP), measured via electroencephalography during electrical stimulation of the tibial nerve.
Timepoint [6] 412741 0
Baseline and at 3, 6, 9, and 12 months from the start of the intervention
Secondary outcome [7] 412742 0
Sensory integrity of somatosensory pathways, as assessed by quantitative sensory testing (QST)
Timepoint [7] 412742 0
Baseline and at 3, 6, 9, and 12 months from the start of the intervention
Secondary outcome [8] 412743 0
Sexual function as measured by Female Sexual Function Index (FSFI), females only; and International Index of Erectile Function (IIEF)-15, males only.
Timepoint [8] 412743 0
Baseline, 3, 6, 9, and 12 months from the start of the intervention.
Secondary outcome [9] 412744 0
Bladder function as assessed by Patient-reported Neurogenic Bladder Symptom Score (NBSS)
Timepoint [9] 412744 0
Baseline, 3, 6, 9, and 12 months from the start of the intervention.
Secondary outcome [10] 412745 0
Bowel function as assessed by Neurogenic Bowel Dysfunction (NBD) score
Timepoint [10] 412745 0
Baseline, 3, 6, 9, and 12 months from the start of the intervention.
Secondary outcome [11] 412746 0
Functional performance assessed using the Functional Independence Measure (FIM) questionnaire
Timepoint [11] 412746 0
Baseline, 3, 6, 9, and 12 months from the start of the intervention.
Secondary outcome [12] 413989 0
Functional performance using the Spinal Cord Injury Independence Measure (SCIM) questionnaire.
Timepoint [12] 413989 0
Baseline, 3, 6, 9, and 12 months from the start of the intervention.

Eligibility
Key inclusion criteria
• Motor complete spinal cord injury (based on ASIA Impairment Scale A or B classification)
• Chronic (> 2 years post injury), traumatic spinal cord injury
• Ability to participate in regular physical activity
• Must sign Informed Consent prior to any study related procedures
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Osteoporosis with a T-Score < -4.0
• Existing selective serotonin reuptake inhibitors (antidepressants), monoamine oxidase inhibitors (antidepressants), or other psychotropic use, unless approved by the participant’s primary physician
• Current amphetamine or recreational drug use
• Fractures in the last 18 months
• History of stem cell therapy in the last 5 years
• Existing baclofen or other antispasmodic use
• Renal impairment
• Hepatic impairment
• Orthopaedic conditions including joint instability
• Pregnancy
• Concurrent significant head injury resulting in psychomotor deficit
• Cognitive impairment that limits capacity
• Epilepsy
• Cardiac pacemakers or defibrillators
• Skin breakdown which would limit ability to sit for 60 minutes
• Any other complications that would prevent participation as determined by the participant’s primary physician

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
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
8
Accrual to date
4
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD

Funding & Sponsors
Funding source category [1] 310740 0
Government body
Name [1] 310740 0
Motor Accident Insurance Commission
Country [1] 310740 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
58 Parklands Dr,
Southport QLD 4215
Country
Australia
Secondary sponsor category [1] 311963 0
None
Name [1] 311963 0
Address [1] 311963 0
Country [1] 311963 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310316 0
Human Research Ethics Committee, Griffith University
Ethics committee address [1] 310316 0
Ethics committee country [1] 310316 0
Australia
Date submitted for ethics approval [1] 310316 0
Approval date [1] 310316 0
11/11/2019
Ethics approval number [1] 310316 0
GU Ref No: 2019/994

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117226 0
Dr Claudio Pizzolato
Address 117226 0
G02 2.03
Griffith University Gold Coast Campus,
58 Parklands Dr,
Southport, QLD 4215
Country 117226 0
Australia
Phone 117226 0
+61 755527066
Fax 117226 0
Email 117226 0
c.pizzolato@griffith.edu.au
Contact person for public queries
Name 117227 0
Kyle Mulholland
Address 117227 0
G02 1.10
Griffith University Gold Coast Campus,
58 Parklands Dr,
Southport, QLD 4215
Country 117227 0
Australia
Phone 117227 0
+61 412366028
Fax 117227 0
Email 117227 0
k.mulholland@griffith.edu.au
Contact person for scientific queries
Name 117228 0
Claudio Pizzolato
Address 117228 0
G02 2.03
Griffith University Gold Coast Campus,
58 Parklands Dr,
Southport, QLD 4215
Country 117228 0
Australia
Phone 117228 0
+61 755527066
Fax 117228 0
Email 117228 0
c.pizzolato@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?
Raw de-identified magnetic resonance imaging data and raw electromyography and electroencephalography data acquired at each assessment points.
When will data be available (start and end dates)?
Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis.
Available to whom?
Access to IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA).
Available for what types of analyses?
Data will be made available for meta analyses and other scientific studies investigating effect of rehabilitation on motor and sensory function after neural trauma.
How or where can data be obtained?
Data can be obtained upon email request to the principal investigator. Please contact Dr Claudio Pizzolato by emailing c.pizzolato@griffith.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.