PHysical Activity and Exercise Outcomes in Huntington's Disease (PACE-HD)
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|ClinicalTrials.gov Identifier: NCT03344601|
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : June 25, 2018
|First Submitted Date ICMJE||October 17, 2017|
|First Posted Date ICMJE||November 17, 2017|
|Last Update Posted Date||June 25, 2018|
|Actual Study Start Date ICMJE||February 16, 2018|
|Estimated Primary Completion Date||October 16, 2019 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT03344601 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||PHysical Activity and Exercise Outcomes in Huntington's Disease|
|Official Title ICMJE||A Longitudinal Cohort Study With Nested Randomised Pragmatic Controlled Trial to Evaluate Physical Activity and Exercise Related Outcomes in People With Huntington's Disease|
Huntington's disease (HD) is a genetic, degenerative neurological disease that affects individuals in their third-fourth decade of life and individuals can live 15-20 years with manifest HD. The complex disease symptoms, including motor, cognitive and behavioural impairments, result in loss of functional independence and progressive escalation of healthcare costs. The personal, social and economic consequences of HD are devastating, especially as there are currently no disease modification therapies available.
Environmental factors, including exercise and physical activity, have the potential to minimize the functional impact of HD. Animal models of HD have provided the first evidence that exercise has the potential to delay or alter disease progression. A range of studies in clinical populations have shown that short-term exercise (< 3 months) is well tolerated and has the potential to improve quality of life, fitness and motor impairments in HD. Despite these promising studies, there are critical knowledge gaps that prevent the intelligent application of exercise as a therapeutic intervention in HD. Firstly, there have been no prospective evaluations of the potential role of physical activity and exercise in disease modification in HD. To date, only retrospective data has suggested that lifestyle factors, including sedentary behavior, could negatively affect disease progression in HD. Secondly, it is not known if sustained exercise (> 3 months) is feasible, and if it has the potential to improve cognitive outcomes, such as has been shown in other neurodegenerative diseases. Such longer-term studies are essential to elucidate the potential for exercise to have a disease-modifying effect; the mechanisms through which such improvement may occur have yet to be explored.
In this trial, the investigators will employ a systematic approach for routinely collecting prospective physical activity and fitness data and monitoring physical activity behaviour in 120 individuals with HD. The investigators will use a database to track physical activity and exercise behaviour alongside standardized disease-specific outcome measures during two annual visits. Assessment will incorporate VO2max, a surrogate measure of fitness and a direct measure of oxygen uptake related to central nervous system (CNS) function and structure, and the use of wearable technologies (Gene-activ activity monitors) that capture and quantify dose (frequency, duration, intensity) of physical activity in a large HD cohort. The investigators will further conduct a within-cohort randomized control trial (RCT) of a 12-month exercise intervention in HD, comparing a supported structured aerobic exercise training program to activity as usual. This intervention will also incorporate a physical activity coaching program developed and evaluated by our group with a view to encouraging longer term exercise uptake.
Huntington's disease (HD) is a neurodegenerative disease causing dysfunction and death of medium spiny striatal projection neurons and thus disruption of corticostriatal pathways with resultant impairment of cognition, motor function, and behaviour. These impairments result in decreasing independence in activities of daily living and quality of life even from relatively early in the disease. The potential to develop interventions to facilitate independent living and strategies to manage symptoms is crucial to managing both the personal and economic effects of this devastating disease. Although to date there are no successful pharmacological interventions that are able to slow disease progression, there is now clear emerging evidence of disease specific motor function and general health benefits of shorter exercise in HD. Although it has been possible to successfully deliver exercise and behaviour change interventions in HD over the shorter term, there is now a need to conduct studies that actively facilitate exercise adherence over a longer term (e.g. one year) to realistically begin to assess the impact of physical activity and structured exercise on disease progression.
Therapeutic exercise interventions present an exciting, transformative area of research in neurodegenerative diseases. Addressing motor impairments in neurodegeneration may provide a long-term beneficial effect in delaying disease progression and maximizing functional abilities over a longer period. Loss of independent mobility and care dependency have been shown to be important predictors of nursing home admissions. The potential to develop interventions that facilitate independent living and strategies to manage symptoms is crucial to managing both the personal and economic effects of this devastating disease. Although to date there are no successful pharmacological or other interventions that are able to slow disease progression, there is some suggestion that lifestyle factors, such as activity level and education alongside specific motor training may help to drive compensatory neural networks, that may in turn compensate for the failing brain, and change the course of the disease. Studies to date in HD have relied on retrospective data, and robust evaluation of lifestyle factors contributing to disease progression is needed. If shown to be effective, exercise programs have the potential to be used in combination with disease-modifying drugs, cell replacement therapy or genetic manipulations, when available, to maximize the functional benefits of these interventions by facilitating adaptive neuroplasticity.
The investigators have set out to systematically evaluate the feasibility of exercise and physical activity interventions in people with HD using a two-pronged approach. The first approach evaluated the feasibility of short-term aerobic and strengthening exercise programs in HD. This led to the recently completed study funded by the Gossweiler Foundation, Exert-HD, a 3-month randomized controlled trial of aerobic (performed between 60-85% age predicted heart rate max) and strengthening exercise. Participants in the exercise group demonstrated significantly improved predicted VO2 max and Unified Huntington Disease Rating Scale (UHDRS) modified Motor Scores (mMS), but no effect was seen on cognition or other measures of motor function.This study had high retention and adherence, and was well tolerated by participants. Alongside this, there was the development and evaluation of the feasibility of a behavioural change intervention to increase levels of physical activity (Engage-HD; ISRCTN65378754). The intervention aimed to evaluate the efficacy of a physical activity intervention (6 sessions over 14 weeks) utilizing a workbook-based behavioural change program compared to a social contact control. This study demonstrated improvements in self-reported physical activity, self-efficacy for exercise, and cognition, however no changes were noted for HD-specific motor function.
In PACE-HD the investigators seek to address three issues that naturally arise from the preliminary studies completed to date. First, there has been no evaluation of long-term (e.g. 12 month) aerobic and strengthening exercise interventions in HD. While studies to date have demonstrated improvements in motor and cognitive function in the short term, it is unclear whether exercise behaviour can be maintained over a longer term, and to what degree any improvements in cognition or motor function can be maintained or enhanced with a longer term intervention.
Second, there is a lack of understanding of the role of physical activity in disease progression in HD. Preliminary work has utilized 7 day activity monitors that have improved functionality to obtain more detailed data on physical activity behavior, including light and moderate- vigorous physical activity, sedentary behavior and sleep patterns over the intervention period. In this trial, the investigators will utilize 7 day activity monitors to evaluate activity patterns longitudinally over a year period in a cohort of 120 people with HD. This longitudinal evaluation alongside standardized evaluations of motor, cognitive and functional abilities will aid in validation of wearable activity devices and evaluate how physical fitness and physical activity may be related to disease progression.
Third, there is lack of understanding of the mechanisms by which exercise may achieve its effect in HD. Trials of longer term exercise interventions are difficult to deliver, not least in terms of the complexity of the intervention but also due to the challenges in accurately characterising the different dimensions of real-life physical activity and understanding individual response to exercise. Our preliminary research has shown that exercise has the potential to improve aerobic fitness using measurements of estimated (predicted) VO2max. This trial will incorporate longitudinal assessment of VO2max, a surrogate measure of fitness and a direct measure of oxygen uptake that is related to central nervous system (CNS) function and structure.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This is a 12 month observational study with a nested randomised controlled trial of a physical activity interventionMasking: None (Open Label)
Primary Purpose: Health Services Research
|Condition ICMJE||Huntington Disease|
|Intervention ICMJE||Behavioral: physical activity
The program will consist of 18 face-to-face coaching sessions (~1 hour) over 12 months. The timing of these sessions will be decided between participant and coach. A coaching manual will be used to provide a structured approach to coaching sessions, focussing on physical activity engagement (specifically aerobic and strengthening exercise) and adherence to exercise. The intervention will take place in the participant's home or in a rehabilitation facility at the research site. Each participant will be provided with a choice of exercise equipment options (e.g. exercise bike, weights, therabands), gym membership or use of online exercise resources. Participants will develop physical activity goals that will be monitored and adjusted throughout the program. Physical activity diaries will be completed to record the amount and type of physical activity involvement. Wearable activity monitors will also be used to facilitate/monitor physical activity and sedentary behaviours.
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE||Same as current|
|Estimated Study Completion Date ICMJE||December 31, 2019|
|Estimated Primary Completion Date||October 16, 2019 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Listed Location Countries ICMJE||Germany, Spain, United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03344601|
|Other Study ID Numbers ICMJE||SPON 1631-17|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||Cardiff University|
|Study Sponsor ICMJE||Cardiff University|
|Collaborators ICMJE||CHDI Foundation, Inc.|
|PRS Account||Cardiff University|
|Verification Date||June 2018|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP