Digital Outcome Assessment Using AI Active Gaming and Motion Capture in Friedreich Ataxia

Design and rationale STEP-OUT FA is an observational?observational A study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records., prospective cohort?prospective cohort A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed. study (STROBE-compliant) developing and validating a digital clinical outcome assessment (dCOA) for Friedreich ataxia. It addresses a well-documented limitation in FA therapeutic development: existing semi-quantitative clinical outcome assessments are affected by floor and ceiling effects, limited responsiveness across disease stages, and poor patient-perceived relevance, which have contributed to repeated failures of drug trials to meet primary endpoints?endpoints Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.. The study evaluates whether motor-performance metrics captured during gamified, semi-immersive virtual-reality (VR) tasks, combined with markerless AI motion analysis, can serve as reliable, valid, and responsive outcome measures. Measurement platform The platform is delivered through a standard laptop and integrates three components: (1) FA-adaptable VR gamified tasks (e.g., ball catching, target reaching) with adjustable difficulty; (2) automated extraction of gaming-performance metrics; and (3) a single-camera, patented AI-driven markerless motion-capture system for 3D pose reconstruction (DigiTherapix Ltd), used to derive biomechanical/kinematic metrics. The gaming environment is provided via the MoveHero platform (University of São Paulo). Laboratory validation (healthy controls and FA participants) Validation is conducted at the University of Exeter VSimulator facility against a gold-standard, marker-based full-body motion-capture reference. During a single laboratory visit (~2 hours), participants complete a familiarisation period followed by a ~20-minute session of four movement-based gaming tasks. Concurrent signals are recorded throughout: full-body optical motion capture (reflective markers on shoulders, elbows, knees, ankles, forehead), continuous heart-rate variability via a Delsys ECG?ECG A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged. sensor (baseline?baseline Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them., task, recovery), and functional near-infrared spectroscopy (fNIRS) over the forehead to index cortical activation. Perceived exertion and fatigue (Borg RPE and Borg VAS Fatigue) are collected after each task, and a short semi-structured interview captures usability and acceptability feedback (audio-recorded for later transcription). FA participants additionally complete clinical characterisation at baseline. Home-based longitudinal phase (FA participants only) To evaluate test-retest reliability and responsiveness, FA participants enter a 12-week home phase with monthly self-administered or remotely supported gaming sessions (~20-30 minutes) at Weeks 4, 8, and 12, each accompanied by a brief telehealth check-in with a physiotherapist to confirm continued consent, provide support, and monitor adverse events?adverse events Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.. Data are captured automatically and remotely. A remote follow-up?follow-up The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes. assessment at Week 12 repeats clinical and patient-reported measures and includes a short interview. Analytic approach Concurrent validity is assessed via correlations between digital metrics and established clinical scales; reliability via intraclass correlation coefficients across repeated sessions; and responsiveness via within-subject change and effect sizes, with longitudinal mixed-effects modelling of dCOA trajectories across the home-phase time points. Analyses characterise which individual or composite metrics (gaming-derived versus biomechanical) show optimal measurement properties and best discriminate disease severity. As an exploratory feasibility and validation study establishing proof of concept and psychometric properties, no formal power calculation was performed; the sample size was justified on precision for reliability estimation and on precedent from rare-disease dCOA validation studies. Collaborators and data governance The AI motion-analysis platform is provided by DigiTherapix Ltd (UK) and the gaming platform by the University of São Paulo (Brazil); formal sub-contractor and data-sharing agreements govern intellectual property and data governance. No personally identifiable participant data are transferred outside the UK. Oxford University Hospitals acts as a Participant Identification Centre only.