ANZCTR - Registration

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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]

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

Condition category

Condition code

Neurological

Other neurological disorders

Physical Medicine / Rehabilitation

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]

Treatment: Devices

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Severity of injury, as measured by American Spinal Injury Association (ASIA) Impairment Scale (AIS) assessment

Timepoint [1]

Baseline, and at 6 and 12 months from the start of the intervention

Secondary outcome [1]

Changes in muscle volume, measured via magnetic resonance imaging (MRI)

Timepoint [1]

Baseline, and at 6 and 12 months from the start of the intervention

Secondary outcome [2]

Anatomical changes to the spinal cord measured by magnetic resonance imaging (MRI)

Timepoint [2]

Baseline, and at 6 and 12 months from the start of the intervention

Secondary outcome [3]

Bone density, measured by Dual-energy X-ray absorptiometry (DXA)

Timepoint [3]

Baseline and after 12 months from the beginning of the intervention

Secondary outcome [4]

Quality of life, as measured by World Health Organisation Quality of Life questionnaire (WHOQOL-BREF)

Timepoint [4]

Baseline, and at 3, 6, 9, and 12 months from the start of the intervention.

Secondary outcome [5]

Voluntary muscle activation as measured by surface electromyography

Timepoint [5]

Baseline and at 3, 6, 9, and 12 months from the start of the intervention

Secondary outcome [6]

Somatosensory evoked potentials (SSEP), measured via electroencephalography during electrical stimulation of the tibial nerve.

Timepoint [6]

Baseline and at 3, 6, 9, and 12 months from the start of the intervention

Secondary outcome [7]

Sensory integrity of somatosensory pathways, as assessed by quantitative sensory testing (QST)

Timepoint [7]

Baseline and at 3, 6, 9, and 12 months from the start of the intervention

Secondary outcome [8]

Sexual function as measured by Female Sexual Function Index (FSFI), females only; and International Index of Erectile Function (IIEF)-15, males only.

Timepoint [8]