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

Abstract

ABSTRACTIntroductionHuntington’s 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 & AnalysisFifty 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.Ethics & DisseminationThe 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, 2ndFloor, Lakeside Building, University Hospital of Wales, Cardiff, CF14 4XW). Findings will be disseminated to researchers and clinicians in peer-reviewed publications and conference presentations, and to participants, carers and the general public via newsletters and public engagement activities. Data will be shared with the research community via the Enroll-HD platform.Trial registration & data set:ISRCTN 11906973(https://doi.org/10.1186/ISRCTN11906973)Protocol: 01/11/2023 version 1.7Strengths and limitationsHD-DRUM is a remotely accessible, tablet-based training tool that can be used at home and allows the objective assessment of adherence and training effects.The use of gamification to match users’ practice to a level appropriate to their abilities is expected to increase adherence and acceptability of HD-DRUM by avoiding frustration and boredom due to over- and underchallenge.This trial will assess the feasibility of a future fully powered effectiveness randomised controlled trial and any modifications that may need to be implemented in HD- DRUM.The randomised controlled study design will allow the estimation of training-induced variability of changes in clinical and brain imaging measures, using state-of-the art ultra-strong gradient 3T MRI.Due to the nature of the intervention and limited resources, researchers and participants are not blinded to group allocation.