TarGAITed stimulation for Parkinson's disease

The aim of this study is to examine the effects of non-invasive peripheral coordinated reset stimulation (peripheral CRS), administered to the feet, upon walking impairments on people with Parkinson's Disease (PD). To do this, peripheral CRS – in the form of vibrotactile (Arm 1) or mild electrical stimulation (Arm 2) – will be applied to participants’ feet over five days. Brain imaging, gait analysis and assessments of clinical signs and symptoms will also be performed. Participants will also be re-assessed at 14- and 30-days post-application of peripheral CRS to determine if there are any long-lasting effects. All procedures will be conducted at the Monash Health Kingston Centre, Cheltenham, Victoria. Participants will be randomised to one of the following study arms: (1) Vibrotactile stimulation: Brief vibrations (similar to the notifications delivered by smartphones) will be delivered using a commercial device, manufactured by Engineering Acoustics. This device consists of individual motors and a controller. (2) Electrical stimulation: Brief electrical pulses via electrodes attached to the participant's skin will be delivered using a custom-built device. The current delivered will be up to a maximum of 4.5 mA. This is less than the currents delivered by commercially available transcutaneous electrical nerve stimulation (TENS) devices, which apply electrical stimulation for management of pain. In both study arms, stimulation will be delivered at a level that is perceivable, with pulses in the range of 50-100ms delivered every 0.5-2 seconds for 2 hours. Individual motors (for vibrotactile stimulation) or electrodes (for electrical stimulation) will be placed on 4 separate sites on each foot. Each site is stimulated one at a time using a CRS pattern. Participants will be seated in a comfortable chair with their feet on a foot stool whilst stimulation is being delivered. Participants will also be asked about their perception of stimulation (whether they perceive it or not), and the level of discomfort using a visual analogue scale. Timeline of participation is described below. Each visit is estimated to take 3 to 4 hours. Twelve hours prior to each visit, participants will be asked to cease taking their PD medication. They will be allowed to resume their medication immediately after each session. Participants are also free to go about their typical day-to-day activities after each visit. Initial assessment (Day 0): Participants will be asked to complete an initial visit to assess if the stimulation applied to their feet is reaching the brain. During this visit, a non-CRS pattern of stimulation will be applied while recording electroencephalography (EEG) to ensure cortical responses to stimulation can be seen. The type of stimulation used (i.e., vibrotactile or electrical) will depend on which study arm the participant has been randomised to. EEG is a non-invasive brain imaging technique which measures brain electrical activity using electrodes placed on the scalp. During this visit, participants will also be asked to complete the Gait Disorders Questionnaire (GDQ). This questionnaire is a self-report measure designed to assess walking problems in people with PD. Stimulation days (Days 1 to 5): Individuals who show clear cortical responses to a non-CRS pattern of stimulation on Day 0, will be asked to return up to a week after the initial visit to start five consecutive days of peripheral CRS as described above. EEG recordings, gait analysis and the Unified Parkinson’s disease rating scale (UPDRS) will be performed on Days 1, 3 and 5 prior to any peripheral CRS being administered. The GDQ will also be completed on Day 5 in addition to the aforementioned assessments. Gait analysis is performed by asking participants to walk along a GAITRite walkway (CIR systems Inc., Clifton, NJ) – a flat, 8.3m carpeted strip with integrated sensors, that allows measurements of key gait characteristics such as stride length, stride time and velocity. Part 2 and 3 of the UPDRS will be used to gather clinical ratings of activities of daily living and motor symptoms. Part 2 involves a questionnaire about a participant’s daily life. Part 3 involves asking the participant to perform certain movements (such as finger tapping, toe tapping, standing up from a chair and walking) while being filmed. The footage will then be scored by a clinician. Follow-up visits (14- and 30-days post-stimulation): Participants who complied with the stimulation days will be asked to return 14- and 30-days after their last stimulation day. During these visits, EEG recordings, Gait Disorders Questionnaire, gait analysis and the UPDRS will be performed. Peripheral CRS stimulation will not be given during these days. Compliance with stimulation is defined as completing at least 3 out of the 5 CRS sessions and will be recorded using session attendance checklists.