ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    pace-hd
Previous Study | Return to List | Next Study

PHysical Activity and Exercise Outcomes in Huntington's Disease (PACE-HD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03344601
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : June 25, 2018
Sponsor:
Collaborator:
CHDI Foundation, Inc.
Information provided by (Responsible Party):
Cardiff University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Huntington Disease Behavioral: physical activity Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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 intervention
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official 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
Actual Study Start Date : February 16, 2018
Estimated Primary Completion Date : October 16, 2019
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
No Intervention: Reference Cohort
A 12-month longitudinal evaluation of physical fitness and physical activity assessments in a cohort of individuals with HD (n=60) recruited from the Enroll-HD platform study.
Experimental: Physcial Activity Intervention
Participants will be recruited from the Enroll-HD platform study and will be individually randomised (1:1) to a 12-month physical activity and coaching intervention.
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.

No Intervention: Activity as usual control
Participants will be recruited from the Enroll-HD platform study and will be individually randomised (1:1) to continue with physical activity as usual for 12 months



Primary Outcome Measures :
  1. Data completeness [ Time Frame: 12 months ]
    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.

  2. Recruitment [ Time Frame: 12 months ]
    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.

  3. Retention [ Time Frame: 12 months ]
    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.

  4. Safety [ Time Frame: 12 months ]
    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.

  5. Adherence [ Time Frame: 12 months ]
    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.

  6. Fidelity [ Time Frame: 12 months ]
    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.

  7. Acceptability [ Time Frame: 12 months ]
    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.


Secondary Outcome Measures :
  1. Work rate (measured in Watts) [ Time Frame: Baseline, 6 months (RCT only), 12 months ]
    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.

  2. Rating of perceived exertion (Borg RPE scale) [ Time Frame: Baseline, 6 months (RCT only), 12 months ]
    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.

  3. Heart Rate (beats per minute) [ Time Frame: Baseline, 6 months (RCT only), 12 months ]
    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.

  4. Predicted VO2 Max [ Time Frame: Baseline, 6 months (RCT only), 12 months ]
    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.

  5. 6 minute walk [ Time Frame: Baseline, 6 months (RCT only) and 12 months ]
    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.

  6. HD Pro-Triad [ Time Frame: Baseline and 12 months ]
    This will be used to assess disease specific symptoms including cognitive decline, emotional/behavioural dyscontrol and motor dysfunction.

  7. Brunel Lifestyle Physical Activity Questionnaire [ Time Frame: Baseline, 6 months (RCT only) and 12 months ]
    This is a self-report instrument that measures the planned and unplanned dimensions of lifestyle physical activity.

  8. Gene-activ assessment [ Time Frame: Baseline, 6 months (RCT only) and 12 months ]
    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.

  9. International Physical Activity Questionnaire (Short Form) [ Time Frame: Baseline, 6 months (RCT only) and 12 months ]
    This will be used to assess 7-day physical activity, and to validate with the physical activity monitors

  10. The Clinch Token Transfer Test (C3T) [ Time Frame: Baseline and 6 months ]
    [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.

  11. Q Motor [ Time Frame: Baseline and 12 months ]
    [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.

  12. Lorig Self Efficacy [ Time Frame: Baseline, 6 months (RCT only) and 12 months ]
    [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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03344601


Contacts
Contact: Cheney J Drew, PhD +44 2920214397 DrewC5@cardiff.ac.uk
Contact: Monica Busse, PhD +44 2920687559 BusseME@cardiff.ac.uk

Locations
United States, California
Re+Active Therapy and Wellness Centre/ UCLA Not yet recruiting
Los Angeles, California, United States, 90045
Contact: Brittney Greer    310-933-4803    brittney@re-activept.com   
Contact: Diane Yang    310-206-3356    DDYang@mednet.ucla.edu   
Principal Investigator: Julie Hershberg         
Principal Investigator: Yvette Bordelon, MD         
United States, New York
Teacher's College, Columbia University Recruiting
New York, New York, United States, 10027
Contact: Radhika Desai    212-678-3424    rd2811@tc.columbia.edu   
Contact: Paula Wasserman       pl2032@cumc.columbia.edu   
Principal Investigator: Lori Quinn, PhD         
Germany
George Huntington Institute Not yet recruiting
Münster, Germany, 48149
Contact: Lisa Muratori, PhD       Lisa.muratori@ghi-muenster.de   
Contact: Laura Spital, PhD       laura.spital@ghi-muenster.de   
Principal Investigator: Ralf Reilmann, PhD         
University Hospital Ulm Not yet recruiting
Ulm, Germany, 89081
Contact: Stefanie Uhl, PhD    731 50063081    Stefanie.Uhl@uniklinik-ulm.der@uni-ulm.de   
Contact: Anita Zanotti       Anita.Zanotti@uniklinik-ulm.de   
Principal Investigator: Bernhard Landwehrmeyer         
Spain
Merce de Deu de la Mare Recruiting
Barcelona, Spain, 08035
Contact: Jesus Ruiz       jmruiz.merced@hospitalarias.es   
Principal Investigator: Jesus Ruiz         
Fundacion Jimenez Diaz Not yet recruiting
Madrid, Spain, 28040
Contact: Asuncion Martinez    689463417    asun@euro-hd.net   
Principal Investigator: Teresa Montojo, MD         
Sponsors and Collaborators
Cardiff University
CHDI Foundation, Inc.
Investigators
Principal Investigator: Monica Busse, PhD Cardiff University
Principal Investigator: Lori Quin, PhD Teacher's College, Columbia University

Responsible Party: Cardiff University
ClinicalTrials.gov Identifier: NCT03344601     History of Changes
Other Study ID Numbers: SPON 1631-17
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The final study data will be shared with the CHDI Foundation Inc.
Time Frame: Data will become available at the conclusion of the study after the primary study results have been published in an open acces journal.
Access Criteria: Applications for the dta must be made to CHDI

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Huntington Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dementia
Chorea
Dyskinesias
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Cognition Disorders
Neurocognitive Disorders
Mental Disorders