PHysical Activity and Exercise Outcomes in Huntington's Disease

NCT03344601 | Unknown

• 1 other identifier: SPON 1631-17
• Study Type: interventional
• Target: 116
• Locations: 3 countries
• Sites: 6

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.

Conditions

Huntington Disease

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (12)

• Work rate (measured in Watts)

  Baseline, 6 months (RCT only), 12 months

• Rating of perceived exertion (Borg RPE scale)

  Baseline, 6 months (RCT only), 12 months

• Heart Rate (beats per minute)

  Baseline, 6 months (RCT only), 12 months

• Predicted VO2 Max

  Baseline, 6 months (RCT only), 12 months

• 6 minute walk

  Baseline, 6 months (RCT only) and 12 months

Study Arms (3)

Reference Cohort

NO INTERVENTION

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.

Physcial Activity Intervention

EXPERIMENTAL

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

Activity as usual control

NO INTERVENTION

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

Interventions

physical activity BEHAVIORAL

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.

Physcial Activity Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cardiff University: lead
• CHDI Foundation, Inc.: collaborator

Study Sites (6)

Re+Active Therapy and Wellness Centre/ UCLA

Los Angeles, California, 90045, United States

Location

Teacher's College, Columbia University

New York, New York, 10027, United States

Location

George Huntington Institute

Münster, 48149, Germany

Location

University Hospital Ulm

Ulm, 89081, Germany

Location

Merce de Deu de la Mare

Barcelona, 08035, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Related Publications (3)

• Quinn L, Playle R, Drew CJG, Taiyari K, Williams-Thomas R, Muratori LM, Hamana K, Griffin BA, Kelson M, Schubert R, Friel C, Morgan-Jones P, Rosser A, Busse M; PACE-HD site investigators. 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. Parkinsonism Relat Disord. 2022 Aug;101:75-89. doi: 10.1016/j.parkreldis.2022.06.013. Epub 2022 Jun 29.

  PMID: 35809488 DERIVED

• Drew CJG, Quinn L, Hamana K, Williams-Thomas R, Marsh L, Dimitropoulou P, Playle R, Griffin BA, Kelson M, Schubert R, Muratori L, Reilmann R, Rosser A, Busse M. 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. Phys Ther. 2019 Sep 1;99(9):1201-1210. doi: 10.1093/ptj/pzz075.

  PMID: 31101920 DERIVED

• Rodrigues FB, Quinn L, Wild EJ. Huntington's Disease Clinical Trials Corner: January 2019. J Huntingtons Dis. 2019;8(1):115-125. doi: 10.3233/JHD-190001.

  PMID: 30776019 DERIVED

MeSH Terms

Conditions

Huntington Disease

Interventions

Exercise

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Monica Busse, PhD

  Cardiff University

  PRINCIPAL INVESTIGATOR

• Lori Quin, PhD

  Teacher's College, Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a 12 month observational study with a nested randomised controlled trial of a physical activity intervention

Study Record Dates

• First Submitted: October 17, 2017
• First Posted: November 17, 2017
• Study Start: February 16, 2018
• Primary Completion: April 30, 2020
• Study Completion: August 31, 2020
• Last Updated: November 5, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• 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

Locations

DE (2); US (2); ES (2)