Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000345785
Ethics application status
Approved
Date submitted
24/01/2022
Date registered
25/02/2022
Date last updated
24/02/2023
Date data sharing statement initially provided
25/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Multidisciplinary Therapy Coaching Program For Individuals With Huntington's Disease
Scientific title
Feasibility and Efficacy of a Multidisciplinary Therapy Coaching Program For Individuals With Premanifest and Manifest Huntington's Disease
Secondary ID [1] 298035 0
None
Universal Trial Number (UTN)
U1111-1232-1506
Trial acronym
HERO'S-CP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington's Disease 312494 0
Condition category
Condition code
Neurological 311040 311040 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single-blind (assessor blinded to group allocation), two arm (multidisciplinary therapy coaching program versus lifestyle guidance), randomised controlled trial. This trial will examine the feasibility, safety and therapeutic effects of a multidisciplinary therapy coaching program, compared to lifestyle guidance, for individuals with premanifest and manifest Huntington's disease.

Participants will be randomly assigned to receive the multidisciplinary therapy coaching program or lifestyle guidance by an independent statistician. Participants in both groups will receive 12 months of treatment (multidisciplinary therapy coaching program/lifestyle guidance).

Multidisciplinary Therapy Coaching Program
The multidisciplinary therapy coaching intervention will be designed by an interdisciplinary team of specialists comprising exercise physiologists, neuroscientists, occupational therapists and physiotherapists. The intervention will encompass cardiorespiratory and resistance exercise training, cognitive training and sleep hygiene two exercise training sessions per week and two computerised cognitive training sessions per week at home. Participants will also be asked to maintain good sleep hygiene throughout the study as indicated by the sleep resources provided. To maximise participant adherence and clinical benefits the multidisciplinary therapy coaching program will be structured into distinct cycles comprising of active, tapering and rest weeks. Six cycles, each eight weeks in duration, will be delivered during the intervention period. The intervention will be delivered by trained multidisciplinary therapy coaches (exercise physiologists). Participants will be contacted by a coach on two separate occasions, at the beginning and midway point (4 weeks) of each cycle. The implementation and progress of the program for that cycle as well as the barriers to training and goals for the upcoming cycle will be discussed.

Cardiorespiratory (e.g., swimming, walking, running) and Resistance Exercise Training (e.g., chest press, upright rows)
The exercise training component of the intervention will comprise individualised (i.e., adjusted to cardiorespiratory fitness [percentage of predicted heart rate max: 220-participant age]), block periodised (i.e., systematically organised exercise variation [volume, intensity and use of specific exercises] into mesocycles [eight week blocks]), progressive and autoregulated (i.e., the volume and intensity of training will be adjusted based on the training response and well-being of patients on training days [i.e., muscle soreness and motivation]) aerobic and resistance exercise training. The intervention will comprise six training blocks that are eight weeks in duration. Each training block will comprise of a training phase (weeks 1-6), detraining/deloading phase (week 7) and rest phase (week 8). An additional rest phase (1 week) will be provided every 16 weeks. Participants will be asked to complete two 45 minute exercise training sessions per week.

The intervention will be delivered in the home environment via telehealth applications (Microsoft Teams). The intensity of exercise during training sessions will be prescribed by percentage of predicted heart rate max (cardiorespiratory) and repetitions in reserve (resistance). The exercise program will be monitored by exercise physiologists and an occupational therapist to ensure that participants reach their target rate of perceived exertion (RPE).

Cognitive Training
The cognitive training program will consist of computerised cognitive training. Computerised cognitive training will be undertaken using NeuroNation software. The prescription and dose of computerised cognitive training are informed by previous work and target a number of cognitive domains including working memory, executive control, divided attention and response inhibition, which are compromised early in HD. Training performance will be automatically recorded by the computerised cognitive training software. Cognitive training will be undertaken twice weekly for 45 minutes.

Sleep Hygiene:

The sleep hygiene intervention will comprise expert recommendations on healthy sleep habits (Morton et al 2013). Participants will also be provided with and encouraged to follow sleep hygiene guidelines as formulated in the Principles and Practice of Sleep Medicine. Participants will receive tailored advice from their coach for thirty minutes (via telehealth) at the start of each block on how to integrate sleep hygiene practices into their sleep routine. Adherence will be evaluated via an intervention diary. Participants will be asked to tick each sleep health recommendation that they adhered to on a weekly basis.
Intervention code [1] 314267 0
Rehabilitation
Comparator / control treatment
Participants in the control group will receive lifestyle guidance, including health advice on exercise, cognitive stimulation and sleep. This will be delivered in an individualised manner. Exercise recommendations will be based on the EHDN Physiotherapy Working Group guidelines (as outlined below). Cognitive activity recommendations will be based on existing evidence and be tailored to the interests of individuals (e.g., people interested in learning will be encourage to undertake education courses or learn a new skill).

Lifestyle guidance

Participants allocated to the lifestyle guidance group will receive guideline documents on physical activity, cognitive stimulation, sleep hygiene and nutritional intake.

Physical Activity Guidelines

Participants in the control group will be provided with physical activity recommendations from the Physiotherapy Working Group of the European Huntington Disease Network (EHDN). These guidelines include the following:
1. Effectiveness of aerobic exercise paired with strengthening exercises in persons with Huntington disease: physical therapists should prescribe aerobic exercise (moderate intensity, 55%–90% heart rate maximum) paired with upper and lower body strengthening 3 times per week for a minimum of 12 weeks to improve fitness and to stabilize or improve motor function.

Cognitive Activity Guidelines

Participants will be encouraged to engage in new cognitive activities, including, creating art or craftwork, completing puzzles, knitting and crocheting, attending lectures and/or playing an instrument.

Sleep Hygiene Guidelines

Participants will receive sleep hygiene guidelines as formulated in the Principles and Practice of Sleep Medicine, which is intended to provide information about lifestyle (diet, exercise, substance use, smoking) and environmental factors (light, noise, temperature) that may interfere with or promote sleep.

Participants will receive contact from a multidisciplinary therapy coach for two sessions, at the beginning and midway point of each eight-week cycle (up to 60 minutes in duration). The purpose of this contact is twofold: 1) to assist individuals with engaging in the prescribed multidisciplinary therapy coaching program or lifestyle guidance program and 2) to ensure that regular social contact is maintained and consistent across groups. For safety reasons, participants will be encouraged to contact their coach if extra explanations are required; these extra sessions will be noted.
Control group
Active

Outcomes
Primary outcome [1] 322105 0
Feasibility of multidisciplinary therapy coaching and lifestyle guidance for individuals with Huntington's disease.

Feasibility will be measured by evaluating the recruitment and retention of Huntington's disease participants during the trial, as well as the adherence of Huntington's disease participants to multidisciplinary therapy coaching and lifestyle guidance. The recruitment (number of participants recruited) and retention (number of participants dropouts) of Huntington's disease participants during the trial will be recorded by the chief principle investigator. Adherence to multidisciplinary therapy coaching and lifestyle guidance throughout the trial will be recorded via passive (heart rate data) and an intervention diary.
Timepoint [1] 322105 0
The feasibility of multidisciplinary therapy coaching and lifestyle guidance will be measured throughout the entirety of the trial. Additionally, an interim assessment time point will be included at 16-weeks to assess the feasibility of the trial and the effects of the interventions on mood, sleep health, lifestyle and quality of life outcomes. This interim assessment time point is vital for assessing the overall fidelity of the trial.
Primary outcome [2] 322106 0
Safety throughout multidisciplinary therapy coaching and lifestyle guidance for Huntington's disease participants

The safety of multidisciplinary therapy coaching and lifestyle guidance will be examined by evaluating adverse events, including musculoskeletal injury, cardiovascular events, falls, excessive mental and physical fatigue. Adverse events reported by participants will be recorded by research staff.

Timepoint [2] 322106 0
The safety throughout the multidisciplinary therapy coaching and lifestyle guidance (adverse events and exercise tolerance) will be reported for each training session by participants using an online intervention diary.
Primary outcome [3] 322107 0
Barriers and motivators to engagement in telehealth-delivered multidisciplinary rehabilitation coaching and lifestyle guidance programs, as well as digital health literacy.

Barriers and motivators as well as digital health literacy will be examined via a semi-structured interview and validated questionnaires, including the Mobile Device Proficiency Questionnaire, Wireless Network Proficiency Questionnaire, Computer Proficiency Questionnaire and e-Health Literacy Scale/Questionnaire.
Timepoint [3] 322107 0
The semi-structured interview and digital health literacy questionnaires will be administered before the delivery of study treatments.
Secondary outcome [1] 377351 0
Verbal learning and memory

Verbal learning and memory will be evaluated using the Hopkins Verbal Learning Test-Revised. This is a composite outcome.
Timepoint [1] 377351 0
Verbal learning and memory will be examined with the Hopkins Verbal Learning Test-Revised at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [2] 377352 0
Processing speed


Processing speed will be examined using the Symbol Digit Modalities Test
Timepoint [2] 377352 0
Processing speed will be examined with the Symbol Digit Modalities Test at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [3] 377354 0
Attention, visual scanning and cognitive flexibility

Attention, visual scanning and cognitive flexibility will be examined with the Trail Making Test. This is a composite outcome.
Timepoint [3] 377354 0
Attention, visual scanning and cognitive flexibility will be examined with the Trial Making Test at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [4] 377359 0
Premorbid Intelligence

The National Adult Reading Test will be used to examine premorbid intelligence.
Timepoint [4] 377359 0
Premorbid Intelligence will be evaluated at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [5] 377362 0
Education and Occupation History/Complexity

Education and occupational history/complexity will be evaluated using a customized demographic questionnaire.

This is a composite outcome/Questionnaire.
Timepoint [5] 377362 0
Education and occupation history/complexity will be evaluated at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [6] 377371 0
Quality of life

Quality of life will be evaluated using the HDQLIFE.
Timepoint [6] 377371 0
Quality of life will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [7] 377381 0
Emotional Experience

Emotional experience will be evaluated with the Brief Emotional Experience Scale.
Timepoint [7] 377381 0
Emotional experience will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [8] 377385 0
Cognitive Reserve

Cognitive reserve will be evaluated with the Cognitive Reserve Index.
Timepoint [8] 377385 0
Cognitive reserve will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [9] 377392 0
Motor Control

Motor control will be evaluated using the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS).
Timepoint [9] 377392 0
Motor control will be evaluated at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [10] 377397 0
Economic viability

The economic viability will be evaluated using economically relevant data, including health adjusted life years, medical fees and medication costs and the Work Productivity and Activity Impairment-Specific Health Problem Questionnaire (WPAI-SHP).

This will form a composite score.
Timepoint [10] 377397 0
Economic viability will be evaluated at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [11] 398977 0
Sleep Health

Sleep health will be evaluated using the Sleep Health Index.
Timepoint [11] 398977 0
Sleep health will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [12] 398978 0
Mood state

Mood state will be assessed using the Problem Behaviours Assessment.
Timepoint [12] 398978 0
Mood state will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [13] 398979 0
Physical activity

Physical activity will be evaluated using the Community Healthy Activities Model Program for Seniors (CHAMPS).
Timepoint [13] 398979 0
Physical activity will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [14] 398980 0
Social network

Social network will be evaluated using the PERSNET.
Timepoint [14] 398980 0
Social network will be evaluated at baseline (0 months), after 16 weeks, after 6 months and after 12 months.
Secondary outcome [15] 398981 0
Socioeconomic status

Socioeconomic status will be measured using a customized demographics questionnaire.
Timepoint [15] 398981 0
Socioeconomic status will be evaluated at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [16] 398983 0
Service utilisation

Service utilisation will be determined using the Client Services Receipt Inventory.
Timepoint [16] 398983 0
Service utilisation will be evaluated at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [17] 405922 0
Primary outcome: Tolerance to exercise for multidisciplinary therapy coaching and lifestyle guidance for Huntington's disease participants.
Timepoint [17] 405922 0
Primary outcome: Participant exercise tolerance will be measured using rating of perceived exertion (RPE; Borg Scale, 0-10) after each exercise session.
Secondary outcome [18] 405924 0
Language

The controlled oral word association test will be used to evaluate language.
Timepoint [18] 405924 0
Language will be examined with the Controlled Oral Word Association Test at baseline (0 months), after 6 months and after 12 months.
Secondary outcome [19] 405925 0
Cognitive flexibility

The colour word interference test will be used to evaluate cognitive flexibility.
Timepoint [19] 405925 0
Cognitive flexibility will be examined with the colour word interference test at baseline (0 months), after 6 months and after 12 months.

Eligibility
Key inclusion criteria
Forty-two individuals with premanifest HD (CAG > 39, DBS > 250, UHDRS-TMS < 5) and 42 individuals with early manifest HD (CAG > 39, UHDRS-TMS > 5, TFC > 7) will be recruited for this trial (effect size: f = .25, a = .05 and power (1- ß) = 80%). Participants will be required to provide written and informed consent prior to undertaking any study procedures.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for participants will include concomitant cardiovascular, metabolic, immunological, neurological and musculoskeletal conditions as well as recent or ongoing substance abuse.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Participants will be randomly allocated to multidisciplinary therapy coaching or lifestyle guidance treatment groups by an independent biostatistician. All assessors will be blinded to group allocation. Research staff responsible for administering the interventions will not be blinded to group allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomization stratified by age and medical treatment. Randomization ratio of 1:1 (multidisciplinary therapy coaching and lifestyle guidance)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical Analyses
For the primary outcome, rates of recruitment (numbers consented/eligible), completion (undertaken baseline and follow-up tests), adherence (participant completed sessions/number of sessions), compliance (volume completed/prescribed volume), program tolerance (sessional rating of perceived exertion [RPE] by the patient using the Borg 0-10 scale after every exercise session) and adverse events (number and number per participant hour) will be calculated. Secondary outcomes will be assessed following intention-to-treat principles. Mixed-model repeated measures ANOVA will be conducted to assess changes in secondary outcomes throughout the study. This model allows inclusion of missing data in an intention-to-treat analysis without imputations (e.g. last-observation-carried-forward). If necessary, analysis will be adjusted for baseline levels and potential confounding factors. Normality assumptions will be assessed using the Shapiro-Wilk test. Statistical significance will be set at an alpha level of 0.05. Corrections will be applied to all analysed outcomes to account for multiple comparisons. Effects sizes will be calculated and interpreted based on the following criteria: d = 0.2 small; d = 0.5 moderate; d = 0.8 large.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
27/02/2023
Actual
Date of last participant enrolment
Anticipated
25/03/2024
Actual
Date of last data collection
Anticipated
24/03/2025
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 15352 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 15353 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 28665 0
6009 - Nedlands
Recruitment postcode(s) [2] 28666 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 302564 0
Charities/Societies/Foundations
Name [1] 302564 0
Perpetual Limited
Country [1] 302564 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Perpetual Limited
Address
Exchange Tower, Level 29/2 The Esplanade, Perth WA 6000
Country
Australia
Secondary sponsor category [1] 302472 0
None
Name [1] 302472 0
NA
Address [1] 302472 0
NA
Country [1] 302472 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303209 0
North Metropolitan Health Service
Ethics committee address [1] 303209 0
QEII Medical Centre, T Block, Nedlands WA 6009
Ethics committee country [1] 303209 0
Australia
Date submitted for ethics approval [1] 303209 0
04/05/2021
Approval date [1] 303209 0
18/10/2021
Ethics approval number [1] 303209 0
RGS0000003748

Summary
Brief summary
Study Aims
This study aims to assess feasibility, therapeutic utility and cost effectiveness of multidisciplinary therapy coaching compared to lifestyle guidance for individuals with premanifest and manifest Huntington's disease.

Who is it for?
You may be eligible to participate in this study if you are aged 18 years or older and been diagnosed with premanifest or early stage manifest Huntington's disease.

Study details
Participants will be randomly assigned (by chance) to receive either multidisciplinary therapy coaching or lifestyle guidance. Those in the multidisciplinary therapy coaching will receive personalized exercise, cognitive and sleep hygiene coaching for twelve months. Those in the lifestyle guidance group will receive a booklet containing information on gold standard recommendations on exercise, cognitive and sleep hygiene. All participants will undergo a series of diagnostic and clinical tests, including cognitive, mood, sleep, activities of daily living tests and questionnaires.

Potential study outcomes
It is hoped this research will inform the treatment of individuals with premanifest and manifest HD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92858 0
Dr Travis Cruickshank
Address 92858 0
Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 92858 0
Australia
Phone 92858 0
+61 8 6304 3416
Fax 92858 0
Email 92858 0
[email protected]
Contact person for public queries
Name 92859 0
Dr Travis Cruickshank
Address 92859 0
Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 92859 0
Australia
Phone 92859 0
+61 8 6304 3416
Fax 92859 0
Email 92859 0
[email protected]
Contact person for scientific queries
Name 92860 0
Dr Travis Cruickshank
Address 92860 0
Edith Cowan University, 270 Joondalup Drive, Joondalup, 6027, Western Australia
Country 92860 0
Australia
Phone 92860 0
+61 8 6304 3568
Fax 92860 0
Email 92860 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data for this study will be kept confidential in a re-identifiable format. The identifier code will only be available to study investigators. Group data will only be presented at conferences and in publications


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseHuntington's Disease Clinical Trials Corner: August 2023.2023https://dx.doi.org/10.3233/JHD-239001
N.B. These documents automatically identified may not have been verified by the study sponsor.