Physical activity and exercise outcomes in Huntington's disease (PACE-HD): results of a 12-month trial-within-cohort feasibility study of a physical activity intervention in people with Huntington's disease.

INTRODUCTION: While physical activity (PA) is recognized as important in Huntington's disease (HD) disease management, there has been no long-term evaluation undertaken. We aimed to evaluate the feasibility of a nested (within cohort) randomized controlled trial (RCT) of a physical therapist-led PA intervention. METHODS: Participants were recruited from six HD specialist centers participating in the Enroll-HD cohort study in Germany, Spain and U.S. Assessments were completed at baseline and 12 months and linked to Enroll-HD cohort data. Participants at three sites (cohort) received no contact between baseline and 12 month assessments. Participants at three additional sites (RCT) were randomized to PA intervention or control group. The intervention consisted of 18 sessions delivered over 12 months; control group participants received no intervention, however both groups completed monthly exercise/falls diaries and 6-month assessments. RESULTS: 274 participants were screened, 204 met inclusion criteria and 116 were enrolled (59 in cohort; 57 in RCT). Retention rates at 12-months were 84.7% (cohort) and 79.0% (RCT). Data completeness at baseline ranged from 42.3 to 100% and at 12-months 19.2-85.2%. In the RCT, there was 80.5% adherence, high intervention fidelity, and similar adverse events between groups. There were differences in fitness, walking endurance and self-reported PA at 12 months favoring the intervention group, with data completeness >60%. Participants in the cohort had motor and functional decline at rates comparable to previous studies. CONCLUSION: Predefined progression criteria indicating feasibility were met. PACE-HD lays the groundwork for a future, fully-powered within cohort trial, but approaches to ensure data completeness must be considered. CLINICALTRIALS: GOV: NCT03344601.

Objectively characterizing Huntington's disease using a novel upper limb dexterity test.

BACKGROUND: The Clinch Token Transfer Test (C3t) is a bi-manual coin transfer task that incorporates cognitive tasks to add complexity. This study explored the concurrent and convergent validity of the C3t as a simple, objective assessment of impairment that is reflective of disease severity in Huntington's, that is not reliant on clinical expertise for administration. METHODS: One-hundred-and-five participants presenting with pre-manifest (n = 16) or manifest (TFC-Stage-1 n = 39; TFC-Stage-2 n = 43; TFC-Stage-3 n = 7) Huntington's disease completed the Unified Huntington's Disease Rating Scale and the C3t at baseline. Of these, thirty-three were followed up after 12 months. Regression was used to estimate baseline individual and composite clinical scores (including cognitive, motor, and functional ability) using baseline C3t scores. Correlations between C3t and clinical scores were assessed using Spearman's R and visually inspected in relation to disease severity using scatterplots. Effect size over 12 months provided an indication of longitudinal behaviour of the C3t in relation to clinical measures. RESULTS: Baseline C3t scores predicted baseline clinical scores to within 9-13% accuracy, being associated with individual and composite clinical scores. Changes in C3t scores over 12 months were small ([Formula: see text] ≤ 0.15) and mirrored the change in clinical scores. CONCLUSION: The C3t demonstrates promise as a simple, easy to administer, objective outcome measure capable of predicting impairment that is reflective of Huntington's disease severity and offers a viable solution to support remote clinical monitoring. It may also offer utility as a screening tool for recruitment to clinical trials given preliminary indications of association with the prognostic index normed for Huntington's disease.

The development of PAT-HD: A co-designed tool to promote physical activity in people with Huntington's disease.

BACKGROUND: Huntington's disease (HD) is a genetic condition resulting in movement, behavioural and cognitive impairments. People with HD have low levels of physical activity which may be compounded by insufficient support from health-care professionals. OBJECTIVE: To evaluate the initial acceptability of a co-designed tool used within a HD clinic to promote physical activity. DESIGN: Co-design of a physical activity tool; acceptability evaluation. SETTING AND PARTICIPANTS: Co-design included people with HD and health-care professionals. Acceptability was evaluated in a HD clinic in the UK. MAIN VARIABLES STUDIED: A physical activity tool was co-designed and used within a HD clinic. MAIN OUTCOME MEASURE: Acceptability as assessed by semi-structured interviews with members of the HD clinic. RESULTS: Forty people visited the HD clinic; 19 were given physical activity advice. Themes around who, where and how promotion of physical activity could take place were identified; concepts of benefits and barriers were threads through each theme. DISCUSSION: We describe for the first time the co-design of a HD specific physical activity tool. Our associated acceptability study emphasizes the importance of individualized planning of physical activities in complex neurodegenerative conditions. Perceived barriers were time and lack of knowledge of local resources. CONCLUSIONS: A simple tool can support conversations about physical activity with people with HD and is an aid to individualized goal setting. Exploring the use of PAT-HD within a community setting and development of support systems for health-care professionals and support workers who are in regular contact with people with HD is required.

An exploration of physical activity experiences throughout the Huntington's disease journey: supporting development of theoretically underpinned complex interventions.

PURPOSE: Huntington's disease is an autosomal dominant neurodegenerative disease. Progressive physical, behavioural and cognitive impairments cause loss of independent function. Physical activity interventions are important components of comprehensive intervention strategies and may help alter the functional decline trajectory. Qualitative research has an important role to play in developing theoretically sound, well-defined physical activity interventions in Huntington's disease. MATERIALS AND METHODS: Eight focus groups were conducted with people with prodromal to late stage Huntington's disease, caregivers (family members/formal), and healthcare professionals. An analytical coding framework was developed from the data and Levanthal's self-regulation model to assist analysis. RESULTS AND CONCLUSIONS: Key themes were identified: evolving representations of Huntington's disease and physical activity; varying social environment of the person with Huntington's disease and the impact on physical activity; achieving physical activity participation while coping with the nuances of Huntington's disease. Levanthal's model facilitated understanding of physical activity experiences, however with progression, self-regulation of activities needs to become more collaborative with caregivers. A modified self-regulation model specific to physical activity in Huntington's disease is presented. Using a novel approach to generate new understanding of physical activity across the Huntington's disease lifespan facilitated development of an original and significant theoretical foundation to underpin development of a range of much needed physical activity and exercise interventions in Huntington's disease.Implications for rehabilitationSocial and familial context of individuals with HD is a key consideration for health care professionals supporting physical activity participation.Strategies such as using physical activity as a way of achieving control and adjusting expectations can help people with HD to continue to be active.People with HD adapt physical activity from high level to more functional activities with symptom progression.

Exploration of a Co-Production Approach to Developing a Walking Group with People with Huntington's Disease.

BACKGROUND: People with Huntington's disease (HD) struggle to maintain regular physical activity despite evidence of the benefits of exercise. This study aimed to evaluate the experiences of people who co-produced a walking group for people with HD. METHODS: Three people with HD, a specialist HD advisor (sHDA), two project officers from Let's Walk Cymru (LWC) and the research team co-produced and participated in a walking group for people with HD. A walking group for people with HD was supported weekly by LWC for eight weeks and fortnightly for a further 12 weeks. Semi-structured interviews were undertaken with three people with HD, a sHDA and two project LWC project officers. Interviews were transcribed verbatim and analysed using thematic analysis. FINDINGS: Interviews identified six themes across participants: "organisation and planning"; "purpose of the walks"; "benefits"; "barriers", "the group" and "the future". People with HD enjoyed participating in the walks and reported increased confidence to be more active outside the home. All participants noted challenges including apathy, diminished planning skills, social stigma and motor problems specific to HD; people with HD perceived a lack of influence in relation to co-planning and co-execution of the walking group. CONCLUSIONS: The walking group was perceived as enjoyable, beneficial, and motivational. This is the first study to report co-production of a walking group with people with HD and the findings suggest that further research is needed to adapt models of co-production for people with a long-term complex condition.

Physical Activity and Exercise Outcomes in Huntington Disease (PACE-HD): Protocol for a 12-Month Trial Within Cohort Evaluation of a Physical Activity Intervention in People With Huntington Disease.

BACKGROUND: Exercise is emerging as an important aspect in the management of disease-related symptoms and functional decline in people with Huntington disease (HD). Long-term evaluation of physical activity and exercise participation in HD has yet to be undertaken. OBJECTIVE: The objective is to investigate the feasibility of a nested randomized controlled trial (RCT) alongside a longitudinal observational study of physical activity and exercise outcomes in people with HD. DESIGN: This will be a 12-month longitudinal observational study (n = 120) with a nested evaluation of a physical activity intervention (n = 30) compared with usual activity (n = 30) using a "trial within a cohort" design. SETTING: The study will take place in HD specialist clinics in Germany, Spain, and the United States, with intervention delivery in community settings. PARTICIPANTS: The participants will have early-mid-stage HD and be participating in the Enroll-HD study. INTERVENTION: This will be a 12-month physical activity behavioral change intervention, delivered by physical therapists in 18 sessions, targeting uptake of aerobic exercise and increased physical activity. MEASUREMENTS: All participants (n = 120) will complete Enroll-HD assessments (motor, cognitive, behavioral, and quality of life) at baseline and at 12 months. Additional Physical ACtivity and Exercise Outcomes in Huntington Disease (PACE-HD) assessments include fitness (predicted maximal oxygen uptake [V o2max]), self-reported and quantitative measures of physical activity, disease-specific symptoms, and walking endurance. RCT participants (n = 60) will complete an additional battery of quantitative motor assessments and a 6-month interim assessment. Enroll-HD data will be linked to PACE-HD physical activity and fitness data. LIMITATIONS: The limitations include that the embedded RCT is open, and assessors at RCT sites are not blinded to participant allocation. CONCLUSION: PACE-HD will enable determination of the feasibility of long-term physical activity interventions in people with HD. The novel "trial within a cohort" design and incorporation of data linkage have potential to reduce participant burden. This design could be applied to other neurological diseases and movement disorders where recruitment and retention are challenging.

A randomized, controlled trial of a multi-modal exercise intervention in Huntington's disease.

INTRODUCTION: This study aimed to evaluate the feasibility and benefit of a structured exercise intervention in people with Huntington's Disease (HD). METHODS: This study was conducted at 6 sites, and participants were randomized into either exercise or control (usual care) groups, and were assessed at baseline, 13 and 26 weeks. The intervention was a 12 week, three times per week progressive exercise program, including aerobic (stationary cycling) and upper and lower body strengthening exercise with tapered 1:1 support for 20 of 36 sessions. RESULTS: 314 adults were assessed for eligibility: 248 did not meet inclusion criteria, 34 declined, and 32 were recruited and randomized. Three individuals in the intervention group were withdrawn within the first month due to concomitant medical conditions, resulting in 14 participants in intervention and 15 in control groups. There were two AEs in the intervention group, both related to previous medical conditions, and there were two SAEs, both in the control group. The intervention group had better fitness (predicted VO2 max difference: 492.3 ml min-1, 95% CI: [97.1, 887.6]), lower UHDRS mMS (difference 2.9 points, 95% [-5.42, -0.32]) and lower weight at Week 13 (difference 2.25 kg, 95% CI: [-4.47, -0.03]). CONCLUSION: This study demonstrates that a short-term exercise intervention is safe and feasible. Individuals with HD may benefit from structured exercise, and intensity, monitoring and support may be key factors in optimizing response. Larger scale trials are now required to fully elucidate the extended clinical potential of exercise in HD. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11392629.

Motor-cognitive dual-task deficits in individuals with early-mid stage Huntington disease.

BACKGROUND: Huntington disease (HD) results in a range of cognitive and motor impairments that progress throughout the disease stages; however, little research has evaluated specific dual-task abilities in this population, and the degree to which they may be related to functional ability. OBJECTIVES: The purpose of this study was to a) examine simple and complex motor-cognitive dual-task performance in individuals with HD, b) determine relationships between dual-task walking ability and disease-specific measures of motor, cognitive and functional ability, and c) examine the relationship of dual-task measures to falls in individuals with HD. METHODS: Thirty-two individuals with HD were evaluated for simple and complex dual-task ability using the Walking While Talking Test. Demographics and disease-specific measures of motor, cognitive and functional ability were also obtained. RESULTS: Individuals with HD had impairments in simple and complex dual-task ability. Simple dual-task walking was correlated to disease-specific motor scores as well as cognitive performance, but complex dual-task walking was correlated with total functional capacity, as well as a range of cognitive measures. Number of prospective falls was moderately-strongly correlated to dual-task measures. CONCLUSIONS: Our results suggest that individuals with HD have impairments in cognitive-motor dual-task ability that are related to disease progression and specifically functional ability. Dual-task measures appear to evaluate a unique construct in individuals with early to mid-stage HD, and may have value in improving the prediction of falls risk in this population.