Retraining Gait in Parkinson's Disease Via a Personalised App

In the UK, falls cost the NHS \>£2billion/year. Parkinson's disease (PD) is one of the most common and progressive neurological disorders, with prevalence projected to double in the next 30-years. PD increases fall risk through walking/gait disturbances, with gait variability related to an increased falls rate/risk. Approximately 60% of people with PD (PwPD) encounter many falls annually. To better understand underlying causes of falls, a gait assessment is undertaken to develop bespoke and targeted/personalised strategies to minimise fall risk.

Instrumenting fall risk Typically, a gait assessment is undertaken by visual inspection, where a physiotherapists tacit expertise/experience enables the identification of obvious and/or subtle gait disturbances. However, reliance on visual observation alone introduces inconsistency/discrepancies in designing fall reduction strategies. To overcome, digital technologies have been investigated e.g., instrumented walkways provide high-resolution gait data to inform retraining via auditory cueing (e.g., stepping to a metronome beat) but they are very costly and bulky to use in most PD services. Regardless, PwPD perceive metronome cueing as monotonous while musical alternatives lack personalisation. Accordingly, there is a need to develop and adopt affordable, pervasive and scalable approaches that are personalised and engaging.

Lab on a phone Technologies that are scalable and easily accessible could facilitate personalised fall reduction programs anywhere. Smartphones are ubiquitous to facilitate near real-time intervention. This study uses our novel app (CuePD), designed to provide cross-platform (i.e., iOS and Android) scalable and personalised auditory cueing for gait retraining to reduce fall risk. CuePD's gait and music algorithms are validated to assess and retrain gait in PwPD within a lab (87-99% accuracy). This project's aim is to deploy CuePD in the home/community, to determine its efficacy as an everyday gait retraining tool. The project is a feasibility randomized controlled trial (RCT) to inform a future grant involving a multicentre observer blind parallel group RCT.

Research questions and hypotheses

* Principal question: Is a personalised home/community gait retraining programme via CuePD feasible and more effective to reduce fall risk than advice about improving gait/walking (i.e., usual care) in people with Parkinson's disease (PwP)?

o Primary hypothesis - CuePD will be feasible and beneficial compared to advice about improving mobility (usual care) to reduce fall risk. * Secondary questions: What is the cost-effectiveness and cost utility of CuePD compared with advice about improving mobility and usual care to reduce fall risk for PwP? What are participants' experiences of CuePD and which factors influence uptake of, and adherence to the programme? o Secondary hypothesis - CuePD will be cost-effective with positive experiences for encouragement of continued use.

Key goals

1. Assess CuePD's feasibility and effectiveness to improve gait and reduce fall risk in the home. 2. Understand how PwP use and value CuePD, to explore (via suggested guidance) how they incorporate it into daily life (home, community). 3. Lay groundwork for larger RCT by collecting data and insights to support future scaling and seamless integration of CuePD into daily life.

Research objectives Accordingly, those objectives (overlapping with goals) will guide the trial structure, including recruitment, randomisation, protocols, and post-intervention analysis.

* The primary objective will assess CuePD's efficacy to improve gait characteristics (stride length, cadence, gait speed and stride time coefficient of variation, CoV) and thereby reduce fall risk. * Secondary objectives are to (i) assess experience, usability factors and adherence to the CuePD intervention and (ii) determine cost-effectiveness and cost utility of CuePD.

Design This is a pragmatic, prospective, parallel observer blind, feasibility RCT to evaluate (i) gait retraining efficacy and (ii) cost-effectiveness, of CuePD versus advice (usual care) over a twelve/12-week period. It will have an allocation ratio of 1:1.

Sample size The sample size is based on a 0.01 significance level, 90% power, and an expected standardised response mean (SRM, a unitless value) of 1.0 for gait speed. Accordingly, 15-participants/group will be recruited (i.e., 30-participants total for a two-group comparison). However, to allow for a 25% attrition rate at 3-months, 40-participants will be recruited across both groups (i.e., 20/group) \[1\].

Randomisation + allocation concealment Participants will be allocated into control or treatment/CuePD using simple randomisation. Randomisation will be by a computer generated random number sequence and will be conducted by the researcher to support the successful blinding of the outcome observer (name1) for the intervention duration. Once allocation has occurred, the outcome observer (name1) will receive a blinded email confirming the participant number, and the outcome assessor (name2, assessing duties) will receive an un-blinded email confirming participant number and allocation from the researcher. To maintain observer blindness throughout the study period, participants will be requested not to discuss the intervention with the outcome observer.

Groups

* Control: Participants will receive usual care consisting of (co-designed by PwP) educational materials focused on maintaining good walking/gait. Materials will provide information on gait/walking factors contributing to falls, practical tips for enhancing gait, and guidance on maintaining mobility. Materials will be distributed to participants/PwP in digital and print formats to accommodate varying preferences, ensuring accessibility. Digital versions will be sent via email, enabling PwP to view them on electronic devices, while printed copies will be handed directly to participants at baseline (via an information pack). This dual-format distribution aims to enhance engagement with the content, ensuring PwP can readily access, and use, the information to manage their condition effectively and reduce fall risk. Materials will be sourced from public facing information via (i) NICE Guidelines \[2\], (ii) Parkinson's UK \[3\], (iii) Parkinson's Foundation \[4\], (iv) Michael J. Fox Foundation \[5\] and (v) NHS \[6\]. Participants will receive weekly calls to check adherence and safety. * CuePD: The intervention arm (using CuePD) to deliver personalised musical cueing to retrain gait and reduce fall risk in PwP. CuePD leverages auditory stimulation via preferred music (i.e., PwP chooses their favourite songs/music) that is selected to match a new/required tempo (i.e., walking cadence) based on PwP baseline stepping cadence to improve gait outcomes such as stride length \[7-9\]. Cadence can be increased from +1% to +10% where a selection algorithm picks music based on its tempo (i.e., beats/minute matching equivalent cadence). Participants will be instructed how to use CuePD and given a waist attachment to wear their smartphone on the lower back, based on open and clinically validated algorithms to interpret inertial data at that body location) and wireless headphones for integration into daily routines, Figure 2. Specifically, the participant will be asked to assess their gait twice/week during the 12 weeks by placing the smartphone on their lower back - CuePD will record their gait via validated algorithms. When the participant wants to carry their smartphone as normal (e.g., pocket), they will still be able to listen to their personalised cued music. Participants will receive weekly calls to check adherence and safety but the CuePD will also be able to objectively track adherence (i.e., frequency and duration of use of the app).

Delivery At baseline, participants will be given an onboarding session in person, where they will learn how to use CuePD and discuss how they can integrate use into their daily lives. The session will tailor musical cues to each participant's baseline walking cadence/tempo, create musical playlists and adaptive adjustments (see below) to support gait retraining. Support will be available throughout the 12-week period via a dedicated helpline and email (to the researcher). CuePD integrates with Apple Music so participants will be subscribed to that music streaming service and costs will be reimbursed as well as data streaming costs.

Additional support will include weekly check-ins with a researcher or nurse via telephone, to monitor progress, address concerns/safety, and adjust the intervention as needed e.g., increasing tempo (see below). Weekly phone calls will include open-ended questions, which will be audio-recorded (with informed consent) to explore user experiences in greater depth Participants will also receive an instructional manual and video tutorial. This multimodal approach ensures that participants have the necessary guidance/support to effectively use CuePD and achieve the intervention goals.

* CuePD treatment, development of intervention: At baseline, participants will be encouraged to use CuePD for up to 30mins, 3 times a week which aligns with another successful Parkinson's cueing approach (equating to a total of 36 sessions over 12-weeks) \[10\]. However, a co-design approach has been implemented. whereby our PwP focus group proposed that:

* Participants be asked to use CuePD as often as they can each week and during any time when they undertake community-based walks * If during the 12-weeks the PwP would like to alter the +10% \[11\] from their baseline cadence (e.g., to +7%) then the researcher will enable a new tempo and new music selection. That request for dynamic functionality (faster or slower), stems from a PwP who commented during our focus group: "some days might be better than others and so I'd like the option of going faster". The dynamic function also aligns with a finding from the NIHR-INCLUDE project \[12\]. However, all adjustments will be discussed with the participant and wider research team to ensure PwP safety. * CuePD adherence (e.g., wear time) and exposure time will be monitored via app functionality (like screen time usage used to monitor how often users engage with apps).

Mode of delivery Control and CuePD arms will be delivered by two providers (researcher or nurse). To attention match, control and CuePD groups will be contacted face-to-face (baseline) and subsequently by telephone once/week to check progression and safety. Both groups will keep a falls diary during the entire duration of the project i.e., 12+12-weeks/3-months. All assessments will be conducted in the home.

* Control group sessions will be undertaken independently (by participant/PwP reading educational material) with telephone support as necessary to encourage engagement with materials (maximum 11-phone calls over the 12-week period). * CuePD group will have the same frequency of telephone calls to encourage use of the app and to make any technical adjustments e.g., changing tempo from +10% baseline cadence to a lower number.

Baseline assessment

The researcher/nurse will perform a baseline assessment following consent to participation. For characterisation and to inform treatment development, the following validated tools and data will be collected:

* Montreal Cognitive Assessment (MoCA), evaluates cognitive function (exclude those with impairment, score \<21). MoCA is as a standardised neuropsychological test and is efficient for the rapid screening of global cognitive dysfunction. It examines diverse cognitive domains e.g., executive functions. * Demographic information: Age, sex. * Unified Parkinson's Disease Rating Scale (UPDRS), evaluates motor and non-motor symptoms, consisting of 4-sections, each targeting a specific area of evaluation (i) non-motor experiences that occur during daily living, (ii) motor experiences during daily living (iii) motor

• Fall frequency [Time frame: 24 weeks]
• Cost effectiveness [Time frame: 24 weeks]
• Cost-utility analysis [Time frame: 24-weeks]
• Perceptions [Time frame: 24 weeks]