Digital Outcome Assessment Using AI Active Gaming and Motion Capture in Friedreich Ataxia (STEP-OUT FA)

July 22, 2026 updated by: University of Exeter

Fusion of Therapeutic AI Active Gaming With Motion Capture to Create a Novel Digital Clinical Outcome Assessment (dCOA) in Friedreich Ataxia

Friedreich ataxia (FA) is a rare, inherited condition that progressively affects balance, coordination, and walking. Clinical trials of new FA treatments rely largely on standard clinical rating scales, but these can be tiring for patients, feel disconnected from everyday life, and may not detect small but meaningful changes over time. More objective, sensitive, and patient-relevant ways of measuring movement are needed.

This study is developing and testing a new digital way of measuring movement in FA. Participants play short, movement-based computer games on a laptop while a single camera and artificial-intelligence (AI) software track how they move. The proposition is that the way a person plays these games - their speed, accuracy, and movement quality - can provide objective, meaningful measurements of motor function. In the laboratory, these game-based measurements are compared against a "gold-standard" full-body motion-capture system and against established clinical scales to check how accurate and meaningful they are.

The study involves both people with Friedreich ataxia (across a range of disease severity) and healthy volunteers. People with FA also take part in a 12-week home phase, playing the games at home each month with remote support, so the researchers can examine whether the digital measurements are reliable when repeated and whether they can detect change over time.

The study asks whether these digital, game-based movement measurements are reliable, valid, and sensitive enough to be used as a "fit-for-purpose" digital clinical outcome assessment (dCOA) in future FA clinical trials, and whether patients find the platform acceptable, usable, and relevant to daily life. This is an early-stage feasibility and validation study designed to establish proof of concept rather than to test the effectiveness of a treatment.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Design and rationale STEP-OUT FA is an observational, prospective cohort 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. 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 sensor (baseline, 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. Data are captured automatically and remotely. A remote follow-up 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.

Study Type

Observational

Enrollment (Estimated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Study participants with FA spanning a range of disease severity and functional mobility, recruited across England, together with healthy volunteers of the same age range serving as a comparison group.

Description

Friedreich ataxia group:

  • Aged 12 to 50 years
  • Genetically confirmed Friedreich ataxia
  • Able to sit or stand independently for 5 minutes
  • Able to provide informed consent (or assent with parental consent if under 16 years)
  • Stable medication regimen (no changes in the past 4 weeks)

Healthy control group:

  • Aged 12 to 50 years
  • No history of genetically confirmed Friedreich ataxia
  • Able to sit or stand independently for 5 minutes
  • Able to provide informed consent (or assent with parental consent if under 16 years)

Exclusion Criteria:

  • Friedreich ataxia group:
  • Aged 11 years or younger, or 51 years or older
  • Severe cognitive impairment precluding task comprehension
  • Active seizure disorder, or vestibular dysfunction causing nausea with non-immersive VR
  • Currently participating in an interventional clinical trial
  • No reliable internet connection (where a digital inclusion pack cannot resolve this)
  • Any reason precluding safe participation in moderate-intensity exercise.

Healthy control group:

  • Aged 11 years or younger, or 51 years or older
  • Genetically confirmed Friedreich ataxia
  • Any reason precluding safe participation in moderate-intensity exercise.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Friedreich Ataxia
Participants aged 12-50 with genetically confirmed FA (homozygous GAA expansion or compound heterozygous FXN mutations). Complete the laboratory validation session and a 12-week home-based phase with monthly gaming sessions.
Device: Laboratory validation session (VSimulator)
Single laboratory visit at the University of Exeter VSimulator in which VR active gaming tasks and single-camera AI-driven markerless motion analysis are performed concurrently with gold-standard marker-based full-body motion capture, functional near-infrared spectroscopy (fNIRS), and continuous heart-rate variability (Delsys ECG sensor). Performed once.
Device: Home-based active gaming assessment
Monthly home-based sessions (Weeks 4, 8, 12) in which participants perform the VR active gaming tasks with concurrent single-camera AI-driven markerless motion analysis via a loaned laptop, with automated remote data capture. No marker-based motion capture, fNIRS, or ECG.
Healthy Controls
Participants aged 12-50 without FA, providing reference data for validation. Complete the laboratory validation session only.
Device: Laboratory validation session (VSimulator)
Single laboratory visit at the University of Exeter VSimulator in which VR active gaming tasks and single-camera AI-driven markerless motion analysis are performed concurrently with gold-standard marker-based full-body motion capture, functional near-infrared spectroscopy (fNIRS), and continuous heart-rate variability (Delsys ECG sensor). Performed once.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Concurrent validity of game-based movement performance against the mFARS - Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Spearman correlation coefficient (ρ; unitless) between game-based movement accuracy (Absolute Error), precision (Variable Error), reaction time, movement time and the modified Friedreich's Ataxia Rating Scale (mFARS) total score (range 0-93; higher = greater neurological impairment), in the Friedreich ataxia cohort.
Baseline laboratory visit (Week 0)
Criterion validity of AI markerless motion capture versus marker-based motion capture - Healthy Controls and Friedreich Ataxia
Time Frame: Baseline laboratory visit (Week 0)
Agreement for upper and lower body angular velocity, joint angles and functional range of motion measured concurrently by the single-camera AI markerless system and the gold-standard marker-based motion-capture system.
Baseline laboratory visit (Week 0)
Comparison of the digital COA metrics between healthy control and Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Use of VR game-derived digital metrics (reaction time, movement time, movement accuracy and precision, and AI-derived kinematic metrics such as angular velocity, joint angles and Functional Range of Motion) to compare healthy control and Friedreich ataxia cohort.
Baseline laboratory visit (Week 0)
Responsiveness of digital COA metrics over time
Time Frame: Weeks 0, 4, 8, and 12
Within-subject change scores and effect sizes for digital metrics, analysed with longitudinal mixed-effects modelling of dCOA trajectories across the home-based phase.
Weeks 0, 4, 8, and 12
Patient Global Impression of Change (PGIC)
Time Frame: Week 12
Patient Global Impression of Change, 7-point ordinal scale (1 = very much improved to 7 = very much worse; higher = greater perceived worsening), in the FA cohort.
Week 12
Platform acceptability and usability
Time Frame: Weeks 0, 4, 8, and 12
System Usability Scale (SUS) total score (range 0-100; higher = better usability; ≥70 acceptable, ≥80 excellent).
Weeks 0, 4, 8, and 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortical activation during gaming tasks (fNIRS) - healthy control and Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Changes in cortical haemodynamic response (oxygenated and deoxygenated haemoglobin) measured by functional near-infrared spectroscopy during the gaming session.
Baseline laboratory visit (Week 0)
Autonomic response during gaming tasks (heart-rate variability) - healthy control and Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Heart-rate variability indices derived from continuous ECG recording (Delsys sensor) at baseline, during, and after the gaming session.
Baseline laboratory visit (Week 0)
Perceived exertion (Borg CR10) - healthy control and Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Borg Rating of Perceived Exertion score (range 1-10; higher = greater exertion) after each gaming task.
Baseline laboratory visit (Week 0)
Fatigue (Borg VAS Fatigue) - healthy control and Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Visual Analogue Scale (VAS) for fatigue (range 0-10; higher = greater fatigue) after each gaming task.
Baseline laboratory visit (Week 0)
9-Hole Peg Test completion time - healthy control and Friedreich ataxia cohort.
Time Frame: Baseline laboratory visit (Week 0)
Time to complete the 9-Hole Peg Test (9HPT), measured in seconds (higher = worse manual dexterity; no fixed maximum), averaged across the dominant and non-dominant hands, in the Friedreich ataxia cohort.
Baseline laboratory visit (Week 0)
Gait quality: proportion of good steps (Heel2Toe sensor)
Time Frame: Baseline laboratory visit (Week 0)
Proportion of "good steps" - steps in which the heel strikes first, detected by the Heel2Toe wearable sensor from ankle sagittal-plane angular velocity, expressed as a percentage of total steps taken during a standardised walking task (range 0-100%; higher = better gait quality), in the Friedreich ataxia cohort.
Baseline laboratory visit (Week 0)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Exeter

Collaborators

University of Oxford

Investigators

  • Principal Investigator: Helen Dawes, University of Exeter
  • Study Director: Andrea Nemeth, University of Oxford

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 30, 2026

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

July 17, 2026

First Submitted That Met QC Criteria

July 22, 2026

First Posted (Actual)

July 28, 2026

Study Record Updates

Last Update Posted (Actual)

July 28, 2026

Last Update Submitted That Met QC Criteria

July 22, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STEP-OUT-FA-364818
  • RMC 25-04 (Other Grant/Funding Number: FA Alliance Innovation Fund)
  • 364818 (Registry Identifier: IRAS Number)
  • 25-26-27 (Other Identifier: University of Exeter Sponsor Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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