Cueing-assisted Gamified Augmented-reality Gait-and-balance Rehabilitation at Home for People With Parkinson's Disease: Protocol of a Pragmatic Randomized Controlled Trial Implemented in the Clinical Pathway

Study design This study is a fully blinded two-armed pragmatic RCT, which will be executed in the Netherlands implemented at multiple physical or exercise therapy clinics. The study consists of three in-clinic assessments performed by the participant's own therapist. After a baseline assessment (T0), participants will start with a 6-week usual care control period, followed by a midterm assessment (T1). Subsequently, participants will undergo two weeks of in-clinic familiarization with Strolll AR supervised by their therapist. Then, participants will start with the 6-week Strolll AR intervention at home integrated with usual care, followed by the final in-clinic assessment (T2).

The definition of a pragmatic RCT is that the intervention is tested in a real-world population in a real-world setting (i.e., the clinic), with an appropriate comparison arm (i.e., usual care alone in the current study) and relevant outcomes to determine its effectiveness. Special trial designs can be considered. In this particular pragmatic RCT all participants follow the same T0-control-T1-intervention-T2 procedure, suitable for both between-groups and within-subjects comparisons of the Strolll AR intervention effects as well as for evaluating its clinical feasibility. With regard to the between-groups comparison, participants will be allocated to control (using T0-T1 change data) or intervention (using T1-T2 change data) groups using multiple (n=20) two-armed randomizations. The randomization will be predefined by an independent person using a Matlab script, locked with a date and timestamp, and kept concealed from participants, therapists and researchers. After the final T2 assessment of the last participant, the 20 randomizations of participants over control and intervention groups will be revealed to the researchers and applied in the data analysis. Participants, therapists, and researchers will therefore all be blind to group allocation during the study. This design, in which all participants receive the Strolll AR intervention, also allows for a complementary within-subjects evaluation of the intervention effect (i.e., being less susceptible to between-subjects variation than aforementioned between-groups evaluation), whilst at the same time providing ample information on the clinical feasibility of the Strolll AR platform implemented in the clinical pathway in terms of its safety, adherence, performance and user experience (i.e., from both participants' and therapists' perspectives). Moreover, a design with the same procedure for all participants makes implementation of this study in the clinical pathway easier (hence the term pragmatic RCT) and potentially reduces drop-out rate because no participants are withheld from receiving the intervention due to the randomization.

Procedure and outcomes After enrollment, the study consists of three in-clinic assessments spread out over 14 weeks, demarcating a usual-care control period and a Strolll AR intervention period. Below we describe the procedure for each of these parts of the design.

Participant enrollment: enrollment and informed consent The therapist will inform eligible participants about the study. If people are interested, they will receive a flyer with instructions on how to send their contact details to the researchers. Upon receival of contact details of a potential participant, the researcher will call this person to provide more information about the study. Hereafter, potential participants will receive the participant information letter by mail or email. A week after receiving the participant information letter, the researcher will again call the potential participant to answer any questions and to ask if he or she wants to participate. If so, in- and exclusion criteria will be checked by the researcher (to the extent possible, otherwise criteria will be evaluated during the baseline assessment session T0). Furthermore, the potential participant will be informed that the medication should remain stable during the study. If the potential participant is eligible, he or she will be asked to sign the informed consent form, after which the researcher also signs the informed consent form and notifies the therapist that the person can start with the pragmatic RCT. Written informed consent must be given before commencing with the baseline assessment (T0).

Baseline assessment (T0): characterization and effectiveness The baseline assessment serves to characterize the study sample and to provide baseline values for evaluating the effectiveness of Strolll AR. Study parameters used to characterize the participants are demographics (i.e., age, gender, disease duration) and current medication use (i.e., the Levodopa Equivalent Daily Dose [LEDD]). Questionnaires to describe the participant population are the Montreal Cognitive Assessment [MoCA], Movement Disorders Society Unified Parkinson Disease Rating Scale [MDS-UPDRS], New Freezing of Gait Questionnaire [NFOGQ], Physical Activity Scale for the Elderly [PASE], Cumulative Illness Rating Scale [CIRS], and 12-month falls history. All these outcomes will be collected using online questionnaires, except for the MoCA and MDS-UPDRS part Ia, III and IV, which will be administered in the clinic by the therapist. To be able to evaluate the potential effects of Strolll AR for improving indicators of gait, balance and falls risk, the following standard clinical tests will be administered by the therapists: Timed Up-and-Go test (TUG), Five Times Sit-to-Stand test (FTSTS), 10-meter walk test (10MWT) and Mini Balance Evaluation Scale Test (Mini-BESTest). In addition, participants will fill out the Falls Efficacy Scale International (FES-I).