Huntington Disease Clinical Trial
— PACE-HDOfficial title:
A Longitudinal Cohort Study With Nested Randomised Pragmatic Controlled Trial to Evaluate Physical Activity and Exercise Related Outcomes in People With Huntington's Disease
Verified date | November 2019 |
Source | Cardiff University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 116 |
Est. completion date | August 31, 2020 |
Est. primary completion date | April 30, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Diagnosis of HD, confirmed by genetic testing - Above the age of 18 - A participant (current or newly enrolled) in the Enroll-HD study - Up to and including stage 2 disease status (TFC 7-13) Exclusion Criteria: - Diagnosis of juvenile onset HD - History of co-morbid neurological conditions such as multiple sclerosis or stroke - Acute orthopaedic conditions (within a month) e.g. ankle sprain or fracture - Inability or unwillingness of participant or legal guardian to give written informed consent |
Country | Name | City | State |
---|---|---|---|
Germany | George Huntington Institute | Münster | |
Germany | University Hospital Ulm | Ulm | |
Spain | Merce de Deu de la Mare | Barcelona | |
Spain | Fundacion Jimenez Diaz | Madrid | |
United States | Re+Active Therapy and Wellness Centre/ UCLA | Los Angeles | California |
United States | Teacher's College, Columbia University | New York | New York |
Lead Sponsor | Collaborator |
---|---|
Cardiff University | CHDI Foundation, Inc. |
United States, Germany, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Data completeness | The amount of trial data completed will be recorded. The amount of complete data will be analysed in reference to the amount of data expected for each participant to give a percentage score of data completeness for each participant. This will give an over percentage data completion rate for the whole trial. The percentage of complete data will be looked at in combination with measures of recruitment, retention, safety, adherence, fidelity and acceptability to assess the overall feasibilty of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Primary | Recruitment | Recruitment to target within the pre-defined recruitment period of 9 months will be recorded. This will result in a percentage value of recruitment to target and will be looked at in combination with measures of data completeness, retention, safety, adherence, fidelity and acceptability to assess the overall feasibilty of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Primary | Retention | The retention of participants to the trial will be recorded. The number of participants who actually complete the trial will be compared to the number of participants in the intervention arm expected to complete the trial will be used to determine the percentage retention of participants and will be used in combination with measures of data completeness, recruitment, safety, adherence, fidelity and acceptability to assess the overall feasibilty of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Primary | Safety | All adverse events in the intervention and comparator arms of the nested RCT will be recorded.The total number of adverse events in each arm will be analysed to see if there is a signifcant difference in the number of events between the two arms. Any difference in the number of adverse events between arms will be used in combination with measures of data completeness, recruitment, retention, adherence, fidelity and acceptability to assess theoverall feasibilty of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Primary | Adherence | The adherence of participants to the intervention will be measured using self report diaries and automated activity monitors. These will be analysed to ensure the participants have adhered to the intervention to an acceptable level. The level of adherence of individual participants will be combined to generate an overall percentage adherence score and this will be used in combination with measures of data completeness, recruitment, retention, safety, fidelity and acceptability to assess the feasibility of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Primary | Fidelity | The fidelity of the intervention delivery by therapists will be assessed through the monitoring of three coaching sessions with each participant. Each monitored session will be analysed and scored on a scale of 0-4 (with 0 = not at all and 4=to a great extent) across 4 domains to give an overall score (maximum 16). Fidelity scores for each participant/ coach will be used to generate on overall fidelity score and this will be used in combination with measures of data completeness, recruitment, retention, safety, adherence and acceptability to assess the feasibility of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Primary | Acceptability | The acceptability of the intervention to participants will be assessed in a post-study questionnaire about specific aspects of the intervention and taking part in the trial. The questionnaire will be a combination of answers using a likert scale from 1-5 (1= strongly agree, 5=strongly agree) and free text responses. Quantitative analysis of the responses will give an overall acceptability score per participant which will be used to produce an average accepatability score. This and qualitative analysis of the free text responses will be used in combination with measures of data completeness, recruitment, retention, safety, adherence and fidelity to assess the feasibility of the trial. The trial will be determined to be feasible if the majority of components investigated reach pre-determined criteria. | 12 months | |
Secondary | Work rate (measured in Watts) | This will be measured during stepwise incremental exercise test. The test is performed on a cycle ergometer with participants seated in a standardized position. Participants will attempt to maintain a cadence of 50 revolutions per minute (rpm), starting at 50 Watts and increasing by 25 Watts every two minutes until test termination. The test will be terminated when the participant reaches volitional exhaustion or cadence drops by 10 rpm. At the end of each increment, work-rate (Watts), This will be used with the rating of perceived exertion and heart rate to calculate the predicted VO2 max. | Baseline, 6 months (RCT only), 12 months | |
Secondary | Rating of perceived exertion (Borg RPE scale) | This will be measured during stepwise incremental exercise test. The test is performed on a cycle ergometer with participants seated in a standardized position. Participants will attempt to maintain a cadence of 50 revolutions per minute (rpm), starting at 50 Watts and increasing by 25 Watts every two minutes until test termination. The test will be terminated when the participant reaches volitional exhaustion or cadence drops by 10 rpm. At the end of each increment rating of perceived exertion using the Borg RPE scale (where participants rate their effort on a scale of 1 [very light activity] to 10 [maximal effort activity]). This will be used with Watts and heart rate to calculate the predicted VO2 max. | Baseline, 6 months (RCT only), 12 months | |
Secondary | Heart Rate (beats per minute) | This will be measured during stepwise incremental exercise test. The test is performed on a cycle ergometer with participants seated in a standardized position. Participants will attempt to maintain a cadence of 50 revolutions per minute (rpm), starting at 50 Watts and increasing by 25 Watts every two minutes until test termination. The test will be terminated when the participant reaches volitional exhaustion or cadence drops by 10 rpm. At the end of each increment heart rate will be recorded for analysis will be used with Watts and rating of perceived exertion to calculate the predicted VO2 max. | Baseline, 6 months (RCT only), 12 months | |
Secondary | Predicted VO2 Max | This will be measured during stepwise incremental exercise test. The test is performed on a cycle ergometer with participants seated in a standardized position. Participants will attempt to maintain a cadence of 50 revolutions per minute (rpm), starting at 50 Watts and increasing by 25 Watts every two minutes until test termination. The test will be terminated when the participant reaches volitional exhaustion or cadence drops by 10 rpm. At the end of each increment, work-rate (Watts), rating of perceived exertion (Borg RPE scale) and heart rate will be recorded for analysis and conversion to predicted VO2 max score. | Baseline, 6 months (RCT only), 12 months | |
Secondary | 6 minute walk | The 6-minute walk test will be used as a measure of walking endurance. This test evaluates the distance walked over a 6 minute period, and has been validated for use in HD. | Baseline, 6 months (RCT only) and 12 months | |
Secondary | HD Pro-Triad | This will be used to assess disease specific symptoms including cognitive decline, emotional/behavioural dyscontrol and motor dysfunction. | Baseline and 12 months | |
Secondary | Brunel Lifestyle Physical Activity Questionnaire | This is a self-report instrument that measures the planned and unplanned dimensions of lifestyle physical activity. | Baseline, 6 months (RCT only) and 12 months | |
Secondary | Gene-activ assessment | Research-grade physical activity monitors (Gene-activs) will be used for a 7-day physical activity assessment. Participants will be given the monitors at the consent visit, and will be asked to return them at the baseline visit one week later. They will be requested to wear them for 24 hours a day for the full week, except when showering. Participants will be given the monitors at the end of the assessments, and will be given addressed stamped mailing envelopes to return the monitors one-week later. Data obtained for analysis will include level of overall physical activity, sedentary behavior and sleep patterns. | Baseline, 6 months (RCT only) and 12 months | |
Secondary | International Physical Activity Questionnaire (Short Form) | This will be used to assess 7-day physical activity, and to validate with the physical activity monitors | Baseline, 6 months (RCT only) and 12 months | |
Secondary | The Clinch Token Transfer Test (C3T) | [RCT sites only] This is a dual-task assessment of bilateral, upper motor function that consists of three-coin transfer tasks which increase in difficulty (baseline simple, baseline complex and a dual task). The time taken to pick up and transfer the coins from dominant to non-dominant hand and place into a purpose developed box is recorded. The addition of cognitive load increases the task complexity. | Baseline and 6 months | |
Secondary | Q Motor | [RCT sites only] This was developed in TRACK-HD and TRACK-ON-HD where motor tasks are related to functionally relevant everyday tasks. All Q-Motor assessments are based on the application of pre-calibrated and temperature controlled force transducers and 3D position sensors with very high sensitivity and test-retest reliability across sessions and sites in a multicenter clinical trial. | Baseline and 12 months | |
Secondary | Lorig Self Efficacy | [RCT sites only] The Lorig scale measures self efficacy in people with chronic disease. Specifically the exercise sub-domain will be measured. Participants are asked to rate their confidence from 1 (not at all confident) to 10 (totally confident) against 3 questions related to undertaking exercise. The scores for each question are summated to give an average score. | Baseline, 6 months (RCT only) and 12 months |
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