Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000922774
Ethics application status
Approved
Date submitted
23/06/2022
Date registered
28/06/2022
Date last updated
28/06/2022
Date data sharing statement initially provided
28/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of combined exercise training on exercise intolerance and cardiovascular health outcomes in adults living with atrial fibrillation.
Scientific title
Thinking beyond cardiac limitations: determining role of combined exercise training as a treatment option for novel markers of exercise intolerance in adults living with atrial fibrillation.
Secondary ID [1] 307420 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
atrial fibrillation 326761 0
exercise intolerance 326762 0
impaired microvascular blood flow 326763 0
Condition category
Condition code
Cardiovascular 323989 323989 0 0
Other cardiovascular diseases
Cardiovascular 323990 323990 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combined exercise training (CT): For participants randomised to the CT group, exercise training will be completed 3 days per week for 12 weeks (36 sessions), with 2 sessions per week to be completed as group sessions (no more than 4-5 participants per group) face-to-face supervised sessions with an Accredited Exercise Physiologist in the Institute for Physical Activity and Nutrition's (IPAN) exercise lab and gym and 1 session to be performed as an individual unsupervised session at home. The 2 face-to-face supervised sessions per week will incorporate both aerobic and resistance training components and the 1 unsupervised session per week will be aerobic training only. Session 18 will involve supervised retesting of cardiorespiratory fitness and muscular strength to modify individual exercise prescriptions due to any changes in fitness levels. All supervised exercise sessions will take 45-60 mins, with all unsupervised MIIT sessions taking 20-30 mins in duration.

Moderate-intensity interval training (aerobic training): For the aerobic training component, participants will complete moderate intensity-interval training (MIIT), with a 3 minute warm-up and cool-down to be performed at each session at a light- to moderate-intensity (45-50% HRR, or Borg’s Rating of Perceived Exertion [RPE] of 10-11/20) prior to and immediately following MIIT, respectively. This will involve a gradual increase in intensity during the warm-up and a gradual reduction in intensity during the cool-down to avoid vasovagal events or syncope This will be completed on an aerobic exercise mode of the participant’s choice (e.g. walking, cycling, aerobic stepping, rowing etc.) during supervised and unsupervised sessions. Sessions 1-5: 4x4 minute moderate-intensity intervals (70-75% heart rate reserve [HRR], RPE: “somewhat hard”, 13-14/20), interspersed with 2-minute active recoveries ( or 50-55% HRR or an RPE at “light” exertion, 11-12/20). Sessions 6-11: MIIT will be progressed to 4x5 minute MIIT with 2 minutes of active recoveries at the same prescribed intensities in Sessions 1-5. Sessions 12-17: MIIT will be progressed to 4x5 minute MIIT with 1 minute of active recovery at the same prescribed intensities in Sessions 1-5. Sessions 19-23: will repeat the same exercise prescription of Sessions 1-5, with exercise intensity to be prescribed based off retesting results obtained from Session 18. Sessions 24-29: will repeat the same exercise prescription from Sessions 6-11, with exercise intensity to be prescribed based off retesting results obtained from Session 18. Sessions 30-36: will repeat the same exercise prescription from Sessions 12-17, with exercise intensity to be prescribed based off retesting results obtained from Session 18.

Resistance Training: For the resistance training component of the exercise session exercise prescription will follow a “cluster sets” training model which can be defined as a pre-planned rest period between a single or groups (“cluster”) of repetitions within a set. This is in contrast to traditional resistance training whereby all repetitions within a set are completed in succession without a rest period. Participants will complete 6 resistance training exercises: chest press, seated row, leg press, knee extension, shoulder press and biceps curl. All exercises will be performed 3 sets of 8 repetitions at 70% 1RM or an RPE of 13-14/20 with 1 minute of passive recovery between sets. Each cluster will be performed as 2x4 repetitions with 30 seconds passive recovery in-between. Previous research in cardiac population groups like atrial fibrillation have shown that hemodynamic responses (blood pressure responses) to resistance training are significantly lower and within a safe range when performed at lower repetition ranges, than high repetition ranges (>11 repetitions performed consecutively), regardless of the intensity prescribed. The intensity of the exercises will increase every 2 weeks: Week 3-4, 75% 1RM; Week 5-6 80% 1RM; Week 7-8: retested 70% 1RM; Week 9-10: retested 75% 1RM; Week 11-12: retested 80% 1RM.

Adherence and compliance to exercise training will be determined by: (i) the completion of number of scheduled sessions attended at the gym as well as Polar HR monitoring data entry for the unsupervised MIIT session; (ii) completing the full duration and intensity of the MIIT component as recorded by HR and RPE; (iii) the number of sets and repetitions completed at the prescribed intensity during the resistance training component.
Intervention code [1] 323857 0
Lifestyle
Intervention code [2] 323858 0
Prevention
Comparator / control treatment
Sham-Placebo Control: Those participants randomised to this group will be instructed to perform static and dynamic stretching of the major muscle groups (chest, back, legs, arms, abdominals) for 20 minutes. One session per week will be conducted supervised sessions with an Accredited Exercise Physiologist, with the remaining two session to be completed unsupervised at home. For the supervised session, the participant will have the option for this to be conduct online or face-to-face.
Control group
Placebo

Outcomes
Primary outcome [1] 331789 0
Change in skeletal muscle microvascular blood flow as assessed by contrast-enhanced ultrasound.
Timepoint [1] 331789 0
Baseline repeated measures (pre-exercise, immediately following exercise, 60-mins post-exercise) and 12-weeks post-intervention (>48 hours after the last exercise session) repeated measures (pre-exercise, immediately following exercise, 60-mins post-exercise).
Primary outcome [2] 331790 0
Changes in exercise tolerance as assessed by peak volume of oxygen uptake (VO2 peak ).
Timepoint [2] 331790 0
Baseline, 6 weeks and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [1] 411118 0
Changes in lower body body muscular strength as assessed by one repetition maximum testing of the leg press
Timepoint [1] 411118 0
Baseline, 6-weeks and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [2] 411119 0
Changes in body composition as assessed by dual-energy x-ray absorptiometry (DXA)
Timepoint [2] 411119 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [3] 411120 0
Changes in quality of life as assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) Questionnaire.
Timepoint [3] 411120 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [4] 411121 0
Changes in atrial fibrillation symptom severity as assessed by the Atrial Fibrillation Symptom Severity Scale (AFSS) Questionnaire.
Timepoint [4] 411121 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [5] 411122 0
Changes in Physical Activity Levels as assessed using an accelerometer (ActiGraph wGT3X-BT).
Timepoint [5] 411122 0
Baseline and 12- weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [6] 411123 0
Changes in cardiac function as assessed by cardiac ultrasound.
Timepoint [6] 411123 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [7] 411124 0
Changes in femoral artery blood flow as assessed by ultrasound recording and imaging.
Timepoint [7] 411124 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [8] 411125 0
Changes in arterial stiffness as assessed by applanation tonometry.
Timepoint [8] 411125 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [9] 411280 0
Changes in Sedentary Levels as assessed using an accelerometer (ActiGraph wGT3X-BT).
Timepoint [9] 411280 0
Baseline and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [10] 411281 0
Changes in upper body muscular strength as assessed by one repetition maximum testing of the chest press.
Timepoint [10] 411281 0
Baseline, 6 weeks and 12 weeks post-intervention (>48 hours after the last exercise session).
Secondary outcome [11] 411329 0
Fasting blood glucose as assessed by venous blood sampling.
Timepoint [11] 411329 0
Baseline and 12 weeks post-intervention
Secondary outcome [12] 411330 0
Glycosylated haemoglobin as assessed by venous blood sampling.
Timepoint [12] 411330 0
Baseline and 12 weeks post-intervention
Secondary outcome [13] 411331 0
Total cholesterol as assessed by venous blood sampling.
Timepoint [13] 411331 0
Baseline and 12 weeks post-intervention
Secondary outcome [14] 411332 0
LDL-C as assessed by venous blood sampling.
Timepoint [14] 411332 0
Baseline and 12 weeks post-intervention
Secondary outcome [15] 411333 0
HDL-C as assessed by venous blood sampling.
Timepoint [15] 411333 0
Baseline and 12 weeks post-intervention
Secondary outcome [16] 411334 0
C-reactive protein as assessed by venous blood sampling.
Timepoint [16] 411334 0
Baseline and 12 weeks post-intervention

Eligibility
Key inclusion criteria
Inclusion criteria: (i) clinical diagnosis of atrial fibrillation as confirmed by a physician with supporting electrocardiogram; (ii) physically inactive (<150 mins exercise per week); (iii) 40-80 years old.
Minimum age
40 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: (i) uncontrolled AF (resting heart rate greater than or equal to 110 bpm); (ii) other cardiovascular disease including coronary artery disease or heart valve disease; (iii) pulmonary hypertension; (iv) heart failure or poor ejection fraction ( less than or equal to 50%); (v) critical limb ischemia including peripheral artery disease or previous revascularisation or other surgical treatment for peripheral artery disease; (vi) history of malignancy within past 5 years (except for non-melanoma skin cancers); (vii) uncontrolled hypertension (resting brachial blood pressure greater than or equal to 160/100 mmHg); (viii) Other musculoskeletal conditions and non-cardiovascular barriers to exercise/physical activity; (ix) currently engages in structured exercise or physical activity greater than or equal to 150 minutes per week; (x) successful ablation; (xi) pregnancy/lactation.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be concealed within a sealed opaque envelope which will be given to the participant following baseline data collection and screening.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified-randomisation will be conducted by a study investigator blinded to the participants; this will be completed using an online platform: www.randomization.com. Factors that will be stratified are atrial fibrillation status and body mass index (BMI).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
To detect a significant difference in muscle microvascular function and blood flow between CT and sham-placebo following a 12-week intervention period, a total sample size of 38 (n=19 per group) is required (f=0.23; a=0.05; ß=0.80, f=0.33, accounting for 10% drop out).

A two-way ANOVA with time (pre- and post-intervention) as the within-subjects factor and group (CT vs sham-placebo control) as the between-subjects factor. Significant interaction and main effects will be explored by a Bonferroni post-hoc with corrections for multiple comparisons to determine if significant differences exist between groups for skeletal muscle microvascular function and blood flow, and all other outcomes.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/08/2022
Actual
Date of last participant enrolment
Anticipated
30/01/2025
Actual
Date of last data collection
Anticipated
30/04/2025
Actual
Sample size
Target
38
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 37870 0
3125 - Burwood

Funding & Sponsors
Funding source category [1] 311696 0
University
Name [1] 311696 0
Deakin University
Country [1] 311696 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country
Australia
Secondary sponsor category [1] 313153 0
None
Name [1] 313153 0
Address [1] 313153 0
Country [1] 313153 0
Other collaborator category [1] 282336 0
Individual
Name [1] 282336 0
A/Prof Michelle Keske
Address [1] 282336 0
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country [1] 282336 0
Australia
Other collaborator category [2] 282337 0
Individual
Name [2] 282337 0
Dr. Lewan Parker
Address [2] 282337 0
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country [2] 282337 0
Australia
Other collaborator category [3] 282338 0
Individual
Name [3] 282338 0
Dr. Hannah Thomas
Address [3] 282338 0
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country [3] 282338 0
Australia
Other collaborator category [4] 282339 0
Individual
Name [4] 282339 0
Dr. Andrew Betik
Address [4] 282339 0
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country [4] 282339 0
Australia
Other collaborator category [5] 282340 0
Individual
Name [5] 282340 0
Ms. Sian O'Gorman
Address [5] 282340 0
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country [5] 282340 0
Australia
Other collaborator category [6] 282341 0
Individual
Name [6] 282341 0
Dr. Jennifer Reed
Address [6] 282341 0
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7.
Country [6] 282341 0
Canada
Other collaborator category [7] 282342 0
Individual
Name [7] 282342 0
Ms. Sol Vidal-Almela
Address [7] 282342 0
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7.
Country [7] 282342 0
Canada
Other collaborator category [8] 282343 0
Individual
Name [8] 282343 0
Dr. Andrew Pipe
Address [8] 282343 0
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7.
Country [8] 282343 0
Canada
Other collaborator category [9] 282344 0
Individual
Name [9] 282344 0
Prof. Steve Selig
Address [9] 282344 0
Deakin University Melbourne Campus, 221 Burwood Highway, Burwood, Victoria, 3125.
Country [9] 282344 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311149 0
Deakin University Human Research Ethics Committee (DUHREC)
Ethics committee address [1] 311149 0
Ethics committee country [1] 311149 0
Australia
Date submitted for ethics approval [1] 311149 0
Approval date [1] 311149 0
15/06/2022
Ethics approval number [1] 311149 0
2022-008

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120114 0
Dr Kimberley Way
Address 120114 0
Melbourne Campus Deakin University, 221 Burwood Highway, Burwood, Victoria, 3125.
Country 120114 0
Australia
Phone 120114 0
+61 3 924 68894
Fax 120114 0
Email 120114 0
[email protected]
Contact person for public queries
Name 120115 0
Kimberley Way
Address 120115 0
Melbourne Campus Deakin University, 221 Burwood Highway, Burwood, Victoria, 3125.
Country 120115 0
Australia
Phone 120115 0
+61 3 924 68894
Fax 120115 0
Email 120115 0
[email protected]
Contact person for scientific queries
Name 120116 0
Kimberley Way
Address 120116 0
Melbourne Campus Deakin University, 221 Burwood Highway, Burwood, Victoria, 3125.
Country 120116 0
Australia
Phone 120116 0
+61 3 924 68894
Fax 120116 0
Email 120116 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Only de-identified data of requested variables will be shared of either journal data sharing agreements or researchers who are interested in accessing the data for analyses.
When will data be available (start and end dates)?
Following the primary publication of this study. There is no end date to the availability.
Available to whom?
Only researchers who provide a sound research proposal and methodology to the Principal Investigator may be provided access.
Available for what types of analyses?
Only to achieve the aims in the approved proposal.
How or where can data be obtained?
Contacting the Principal/Chief Investigator, Dr. Kimberley Way: [email protected].


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16461Ethical approval    384264-(Uploaded-23-06-2022-15-21-42)-Study-related document.pdf



Results publications and other study-related documents

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