Protocol for a randomised controlled feasibility trial of HD-DRUM, a rhythmic movement training application for cognitive and motor symptoms in people with Huntingtons disease.

Introduction: Huntingtons disease (HD) is an inherited neurodegenerative disease causing progressive cognitive and motor decline, largely due to basal ganglia (BG) atrophy. Rhythmic training offers promise as therapy to counteract BG-regulated deficits. We have developed HD-DRUM, a tablet-based app to enhance movement synchronization skills and improve cognitive and motor abilities in people with HD. This paper outlines a randomised controlled trial protocol to determine the feasibility of a larger effectiveness trial for HD-DRUM. Additionally, the trial investigates cognitive and motor function measures, along with brain microstructure, aiming to advance our understanding of the neural mechanisms underlying training effects. Methods, Design & Analysis: Fifty individuals with HD, confirmed by genetic testing, and a Total Functional Capacity (TFC) score of 9-13, will be recruited into a two-arm randomised controlled feasibility trial. Consenting individuals with HD will be randomised to the intervention group, which entails eight weeks of at-home usage of HD-DRUM, or a usual-activity control group. All participants will undergo cognitive and motor assessments, alongside ultra-strong gradient (300mT/m) brain microstructural magnetic resonance imaging (MRI) before and after the eight-week period. The feasibility assessment will encompass recruitment, retention, adherence, and acceptability of HD-DRUM following pre-specified criteria. The study will also evaluate variations in cognitive and motor performance and brain microstructure changes resulting from the intervention to determine effect size estimates for future sample size calculations. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ISRCTN 11906973 ### Funding Statement This work was supported by a National Institute for Health Research (NIHR) and Health and Care Research Wales (HCRW) Advanced Fellowship to Claudia Metzler-Baddeley (grant number: NIHR-FS(A)-2022). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study has received favourable ethical opinion from the Wales Research Ethics Committee 2 (REC reference: 22/WA/0147) and is sponsored by Cardiff University (SPON1895-22) (Research Integrity, Governance and Ethics Team, Research & Innovation Services, Cardiff University, 2nd Floor, Lakeside Building, University Hospital of Wales, Cardiff, CF14 4XW). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data will be shared with the research community on request via the Enroll-HD platform.