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Trial registered on ANZCTR


Registration number
ACTRN12623000055606
Ethics application status
Approved
Date submitted
7/01/2023
Date registered
17/01/2023
Date last updated
17/01/2023
Date data sharing statement initially provided
17/01/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does the addition of high-intensity single muscle group training improve exercise training efficiency in heart failure?
Scientific title
Does the addition of high-intensity small muscle mass training result in greater improvements in exercise capacity, physical performance, muscle strength and health-related quality of life outcomes for individuals with heart failure?
Secondary ID [1] 307885 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
heart failure 327532 0
Condition category
Condition code
Cardiovascular 324634 324634 0 0
Other cardiovascular diseases
Physical Medicine / Rehabilitation 325665 325665 0 0
Other physical medicine / rehabilitation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
High-intensity small muscle mass training (HISMT) plus modified standard training (MST): Participants will undertake isolated knee extensor HISMT during twice weekly exercise sessions, with the training load increased as tolerated over the 12-week training period. The HISMT protocol will consist of a series of bilateral, dynamic knee extension exercises against a resistive load using a knee extensor machine. This training will be undertaken as 3 sets of up 25 repetitions, with a concentric-eccentric contraction time ratio of 1:2. During each session, participants will also undertake a modified version of the standard training (ST; described in comparator/control treatment section below) so that the total volume of work is similar to those undertaking ST alone. The perceived levels of exertion (using the Borg 0-10 category ratio (CR) scale), quadriceps muscle fatigue (using the Borg 0-10 CR scale) and knee pain (using a 0-10 integer numerical rating scale; 0 – no pain, 10 – worst pain imaginable) will be ascertained prior to commencing the HISMT protocol and following completion of each set. The aim of the HISMT protocol is to achieve temporary muscle failure at the end of each set (determined by quadriceps muscle fatigue rating of at least 7 on the Borg 0-10 CR scale), without eliciting any adverse signs or symptoms or musculoskeletal pain. The exercise training will be administered by a physiotherapy clinician with a minimum of 10 years experience and undertaken within a face-to-face, group-based outpatient HF rehabilitation program at two sites i.e. Gold Coast Hospital and Health Service (GCHHS) and The Prince Charles Hospital (TPCH). Each training session has capacity for up to 12 patients and is approximately 90 minutes in duration. Adherence to the allocated intervention will be monitored by means of session attendance and completion of the prescribed exercise program.
Intervention code [1] 324355 0
Rehabilitation
Comparator / control treatment
Standard training (ST) alone: Participants will be given the standard centre-based, outpatient rehabilitation program provided by the GCHHS and TPCH HF exercise programs (HFEPs), in which patients attend twice weekly face-to-face, group-based exercise sessions for 12 weeks. The training sessions have capacity for up to 12 patients. During the sessions, patients undertake a combination of upper and lower extremity aerobic- and resistance-based exercises e.g. treadmill walking, stationary bicycle, arm ergometer, sit-to-stand, mini squats, calf raises, bicep curls and wall push-ups. The initial target training intensity range is 11 to 13 as assessed by the Borg 6-20 Rating of Perceived Exertion (RPE) scale, with patients aiming to achieve 12 to 14 at subsequent sessions as tolerated. Observations (heart rate, oxygen saturation and blood pressure, as well as blood glucose levels if required) are taken at the start and on completion of the exercise session. A medical screen is conducted to ensure clinical stability and safety for exercise. Each exercise session is approximately 90 minutes in duration, beginning with a 10-15 minute warm-up of low-intensity aerobic exercise and concluding with a 15 minute cool-down consisting of a low-intensity aerobic exercise and static upper and lower body stretches. The exercise training program is administered by a physiotherapy clinician with a minimum of 10 years experience and supported by nursing staff. After each session, the exercise prescription is reviewed by a physiotherapist and progressed based on the person’s tolerance of their set program and clinical parameters. Adherence to the allocated intervention will be monitored by means of session attendance and completion of the prescribed exercise program.
Control group
Active

Outcomes
Primary outcome [1] 332450 0
Exercise capacity as assessed by the six-minute walk test (6MWT)
Timepoint [1] 332450 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [1] 413619 0
Physical performance as assessed by the timed up and go (TUG) test
Timepoint [1] 413619 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [2] 413620 0
Physical performance as assessed by the 30-second sit-to-stand test (30sec-STST)
Timepoint [2] 413620 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [3] 413621 0
Skeletal muscle strength as assessed by quadriceps maximal voluntary isometric contraction (MVIC) using a hand-held dynamometer
Timepoint [3] 413621 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [4] 413622 0
Skeletal muscle strength as assessed by knee extensor five-repetition maximum (5-RM) on a knee extensor chair
Timepoint [4] 413622 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [5] 413623 0
Skeletal muscle strength as assessed by hand grip strength using a Jamar dynamometer
Timepoint [5] 413623 0
Baseline and 12 weeks after intervention commencement
Secondary outcome [6] 413624 0
Health-related quality of life (QoL) as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Timepoint [6] 413624 0
Baseline and 12 weeks after intervention commencement

Eligibility
Key inclusion criteria
A diagnosis of heart failure (HF) as per the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand HF guidelines (2018);
Clinically stable and deemed suitable to participate in an exercise program;
New York Heart Association (NYHA) class I to III;
Aged 18 years and over.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Comorbid disease, or physical, cognitive or behavioural factors that interfere with or prevent participation in exercise training;
Contraindications to exercise testing or training as per the HF Association/European Association for Cardiovascular Prevention and Rehabilitation position paper (2011).

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a web-based randomisation program
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size of 70 participants was determined using a power calculation and an effect size of 0.65 based on the mean change in six-minute walk distance (6MWD) following a concentric/eccentric HISMT intervention as part of a laboratory-based study undertaken by this research team (unpublished data). This laboratory-based study evaluated the efficacy of two types of isolated knee extensor HISMT protocols (i.e. concentric-only HISMT and concentric/eccentric HISMT) for individuals with HF with reduced ejection fraction (HFrEF). The effect size for the increase in mean 6MWD was 1.30; however, a more conservative value of 0.65 was chosen i.e. half the effect size. Using this approach, and conventional a (0.05) and ß (0.80) values, the required sample size for the study was calculated as 60 participants (i.e. 30 in each training intervention group). Hence, the sample size of 70 participants (i.e. 35 in each group) will account for the calculated sample size, as well as a potential 15% drop-out rate.

Data will be anaylsed using intention-to-treat principle, with the inclusion of all available measures for the participants, regardless of subsequent crossover or non-adherence to the assigned treatment intervention. Descriptive statistics will be presented as numbers and percentages for categorical variables and as means and standard deviation or median and interquartile range for continuous variables according to the normality of distribution. Continuous variables will be screened for normality of distribution using the Shapiro-Wilks test. Between-group participant characteristics will be assessed using independent t-test or a non-parametric equivalent. A one-way analysis of covariance or non-parametric equivalent will be performed to determine changes in dependent variables in response to the training interventions. Pair-wise comparisons using Bonferroni adjustments will be applied when a significant interaction and/or main effect is detected. Wilcoxon signed rank and Mann-Whitney U tests will be performed to determine between- and within-group differences respectively for the QoL data. Statistical significance will be accepted at P < 0.05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
10/01/2023
Date of last participant enrolment
Anticipated
1/10/2024
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
70
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 39233 0
4032 - Chermside
Recruitment postcode(s) [2] 39232 0
4226 - Robina

Funding & Sponsors
Funding source category [1] 312159 0
Hospital
Name [1] 312159 0
Gold Coast Hospital and Health Service (Gold Coast Health and Gold Coast Hospital Foundation Research Grant Scheme 2017-18)
Country [1] 312159 0
Australia
Funding source category [2] 312182 0
Hospital
Name [2] 312182 0
The Prince Charles Hospital (The Prince Charles Hospital Foundation Innovation Grant 2018-19)
Country [2] 312182 0
Australia
Primary sponsor type
Individual
Name
Menaka Louis
Address
Robina Health Precinct, 2 Campus Crescent, Robina, QLD, 4226
Country
Australia
Secondary sponsor category [1] 313705 0
None
Name [1] 313705 0
Address [1] 313705 0
Country [1] 313705 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311550 0
Gold Coast Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 311550 0
1 Hospital Boulevard, Southport, QLD, 4215
Ethics committee country [1] 311550 0
Australia
Date submitted for ethics approval [1] 311550 0
19/01/2018
Approval date [1] 311550 0
23/03/2018
Ethics approval number [1] 311550 0
HREC/18/QGC/20
Ethics committee name [2] 311564 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [2] 311564 0
627 Rode Rd, Chermside, QLD, 4032
Ethics committee country [2] 311564 0
Australia
Date submitted for ethics approval [2] 311564 0
12/07/2018
Approval date [2] 311564 0
20/09/2018
Ethics approval number [2] 311564 0
HREC/18/QPCH/291

Summary
Brief summary
Background: Skeletal muscle alterations significantly contribute to exercise intolerance in heart failure (HF). Small muscle mass training, localised to the quadriceps femoris muscle group, has been proposed as an intervention to target these HF-related changes. The application of this training paradigm in HF is supported by a recent literature review that found improvements in whole-body exercise capacity, quadriceps muscle strength and health-related quality of life (QoL) in those with reduced ejection fraction. Since this training involves only one muscle group, it places a lower demand on the central circulation than whole-body exercise, thereby permitting a near-maximal intensity protocol. Hence, this proposed study will evaluate high-intensity small muscle mass training (HISMT) isolated to the knee extensor muscles in a conventional clinical context, with the aim to determine the additive effects of integrating HISMT within a standard HF rehabilitation program.
Methods: This randomised, controlled, single-blind trial will aim to recruit 70 clinically stable participants aged 18 years and over with a HF diagnosis and New York Heart Association class I to III. Participants will be randomly allocated to either: (i) standard training (ST) alone: combination of upper and lower extremity cardiovascular and resistance-based exercises; or (ii) HISMT plus modified ST: bilateral, isolated knee extensor HISMT in addition to a modified version of the ST, so that the total volume of work will be similar to ST alone. The training interventions will be conducted twice weekly for 12 weeks in an outpatient setting. Outcome measurements will be performed at baseline and following the 12-week intervention period. The primary outcome measure will be exercise capacity (six-minute walk test), with secondary measures being physical performance (timed up and go test and 30-second sit-to-stand test), muscle strength (quadriceps maximal voluntary isometric contraction, knee extensor five-repetition maximum and hand grip strength), and health-related QoL (Kansas City Cardiomyopathy Questionnaire).
Discussion: This study will assess whether there are greater improvements with incorporating knee extensor HISMT within a traditional HF rehabilitation program. It is hypothesised that the addition of HISMT will confer superior outcomes. In addition to extending current knowledge relating to small muscle mass training, the study will provide a unique perspective on the effects of HISMT within routine clinical practice, thus enabling the optimisation of exercise prescription for the HF patient population.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121502 0
Mrs Menaka Louis
Address 121502 0
Robina Health Precinct
2 Campus Crescent
Robina QLD 4226
Country 121502 0
Australia
Phone 121502 0
+61 7 5635 6290
Fax 121502 0
Email 121502 0
Menaka.Louis@health.qld.gov.au
Contact person for public queries
Name 121503 0
Mrs Menaka Louis
Address 121503 0
Robina Health Precinct
2 Campus Crescent
Robina QLD 4226
Country 121503 0
Australia
Phone 121503 0
+61 7 5635 6290
Fax 121503 0
Email 121503 0
Menaka.Louis@health.qld.gov.au
Contact person for scientific queries
Name 121504 0
Mrs Menaka Louis
Address 121504 0
Robina Health Precinct
2 Campus Crescent
Robina QLD 4226
Country 121504 0
Australia
Phone 121504 0
+61 7 5635 6290
Fax 121504 0
Email 121504 0
Menaka.Louis@health.qld.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Deidentified individual participant data relating to published results only
When will data be available (start and end dates)?
For 5 years following main results publication
Available to whom?
Case-by-case basis at discretion of primary sponsor
Available for what types of analyses?
For aims consistent with the approved proposal and IPD meta-analyses
How or where can data be obtained?
Access subject to approval by principal investigator (Menaka Louis; email: menaka.louis@griffithuni.edu.au)


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17738Study protocolEmail correspondence to principal investigator (Menaka Louis; email: menaka.louis@griffithuni.edu.au) menaka.louis@griffithuni.edu.au Intend to be published in peer-reviewed journal



Results publications and other study-related documents

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