Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001071718
Ethics application status
Approved
Date submitted
18/07/2022
Date registered
3/08/2022
Date last updated
8/03/2024
Date data sharing statement initially provided
3/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Rehabilitation after bone marrow transplant- what is the impact on patient outcomes?
The REBOOT trial
Scientific title
The impact of Rehabilitation after bone marrow transplant on physical function outcomes. The REBOOT trial
Secondary ID [1] 305621 0
N/A
Universal Trial Number (UTN)
Trial acronym
REBOOT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignancy 324051 0
Bone Marrow Transplant 324052 0
Condition category
Condition code
Cancer 321565 321565 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The delivery model will be predominately via telehealth consultations but include 2 face to face sessions (at baseline and at approximately 4 weeks) to perform baseline measures, teach use of accelerometer and at week 4 to assess that exercises are being performed optimally. Intervention will commence at the next available session after recruitment (at 30 days +/- 10 working days) but within 2 weeks of recruitment. Delivery of all sessions will be underpinned by behaviour change principles in order to promote adherence to both exercise and nutritional advice and the longer-term maintenance of exercise and a healthy diet. Instructors will be trained by a behaviour change scientist in how to promote goal setting, intrinsic motivation, self-efficacy and habit formation (i.e., key determinants of sustained behaviour change). In addition behaviour change strategies will include action planning, barrier identification/problem solving, self-monitoring of behavioural outcomes (using an activity monitor and diary), relapse prevention/coping planning and providing feedback regarding performance. Participants will be provided with comprehensive and evidence-based behaviour change resources to support self-management. These will be developed specifically for this study.

Prior to commencement of the exercise program, intervention participants will attend an individual 60minute session with the trial dietitian (telehealth or face to face). During this session, a comprehensive nutrition assessment will be completed in order to inform individualised dietary advice to achieve a protein intake of 1.5g/kg body weight, and 25 to 30 kcal/kg/body weight aimed at optimising lean mass and preventing increase in fat mass. While a food-based approach will be utilised, participants will also be instructed to take a powdered whey-based protein supplement (20g protein) taken within 30 minutes of exercise, added to a liquid of their choice to preserve and build muscle mass. Individualised dietary advice will also be provided to modify aspects of participants dietary intake and eating patterns to minimise long-term treatment-related cardiometabolic consequences.

Exercise sessions (60-75 minutes), supervised by a physiotherapist, will be conducted twice weekly for eight-weeks. Remote sessions will be delivered using the telehealth platforms available within the hospital recruitment sites. Exercise via telehealth will include warm up and cool down exercises, interval training for 30 mins and resistance training for 20 minutes. Heart rate and/or BORG RPE will guide exercise intensity (aiming for a moderate-high intensity 4-6/10) and exercise progressed according to current exercise guidelines. Aerobic Exercises via telehealth will include for example, marching on the spot, running on the spot, star jumps, marching with concurrent upper limb exercises. Exercise and rest intervals will be set depending on the initial patient assessment. Resistance exercises will include functional exercises such as sit to stand, heel-raises, squats, step ups, bench push ups, bicep curls, overhead press, shoulder abduction. Resistance exercises will be prescribed from baseline assessment findings (10 repetition maximum) and commenced at 80% of this. Participants will be reminded about diet and whey protein supplementation at each session and adherence will be recorded by the physiotherapist. There will be rolling recruitment to the trial with exercise sessions group based where possible with up to 4 participants.

A home program of moderate level continuous exercise (walking) will be prescribed aiming to exercise on the days not attending group sessions on telehealth. This program will be individualised but aim for walking 30 mins per session, 3-5 days per week. Exercise prescription will follow the Frequency, Intensity, Time and Type (F.I.T.T.) training from baseline assessment findings (e.g., six-minute walk test or BORG RPE). Wearable devices will be provided to participants to track their physical activity levels (step count and activity levels) during the trial.
A fidelity check list designed specifically, will used to measure exercise intensity, frequency and mode after every exercise session. Feasibility data will be collected (eg number of sessions attended) as per process evaluation outcome measures.

At one centre prehabilitation is already usual care. This centre undertakes autologous bone marrow transplant (BMT). Prehabilitation will be provided according to their protocols in the 4-6 weeks prior to BMT. Prehabilitation includes exercise sessions twice weekly until transplant (aerobic and resistance similar to the exercises described above) with design based upon individual assessments and using telehealth or face to face as individual or group sessions and may include dietary advice. These sessions (as part of usual care) will be documented.

At this same centre we will also measure consecutive participant ultrasound muscle mass and quality of rectus femoris thigh muscle at baseline and follow up one (week 9 after rehabilitation program).
Intervention code [1] 322023 0
Rehabilitation
Comparator / control treatment
Both groups will receive usual medical and nursing care after transplant (which does not usually involve exercise or nutritional interventions). At the recruitment hospitals (consistent with broad Australian practice) there is no rehabilitation model of care offered after transplant. Participants will receive usual care face-to-face and printed educational materials about bone marrow transplants from nursing and medical staff. These have been developed specifically by the recruitment hospitals and are part of usual care.
Control group
Active

Outcomes
Primary outcome [1] 329327 0
Health-related quality of life (Physical Function domain of the EORTC QLQ-C30)
Timepoint [1] 329327 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [1] 402152 0

Proportion of participants defined as malnourished based on the Global Leadership on Malnutrition (GLIM) criteria
Timepoint [1] 402152 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [2] 402429 0
Participant dynamic nutritional status and a categorical ranking of malnutrition using Patient-Generated Subjective Global Assessment (PG-SGA)
Timepoint [2] 402429 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [3] 402430 0
Fat-free mass; measured by non-invasive bioimpedance spectroscopy
Timepoint [3] 402430 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [4] 402431 0
Quadriceps point of care ultrasound imaging of rectus femoris muscle (cross sectional area and echogenicity) in consecutive participants at one recruitment site
Timepoint [4] 402431 0
Baseline (Week 0) and Follow-Up 1 (Week 9) after rehabilitation program
Secondary outcome [5] 402432 0
Handgrip muscle strength: bilateral handgrip dynamometry
Timepoint [5] 402432 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [6] 402433 0
Sarcopenia risk screening: SARC-F
Timepoint [6] 402433 0
Baseline (Week 0), Follow-Up 1 (Week 9), Follow-Up 2 (6 months) and Follow-Up 3 (12 months)
Secondary outcome [7] 402434 0
Dietary intake: measured using a 3-day food records and energy requirements estimated from standard equations
Timepoint [7] 402434 0
baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [8] 402435 0
Physical activity - International Physical Activity Questionnaire-short form (IPAQ-SF)
Timepoint [8] 402435 0
Baseline (Week 0), Follow-Up 1 (Week 9), Follow-Up 2 (6 months) and Follow-Up 3 (12 months)
Secondary outcome [9] 402437 0
Physical activity - Accelerometry (worn over a 7-day period during waking hours)
Timepoint [9] 402437 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [10] 402439 0
The number of times the participant can stand from a chair in 30 seconds: 30 Second Sit to Stand test
Timepoint [10] 402439 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [11] 402440 0
Functional exercise capacity: 6-Minute Walk Test
Timepoint [11] 402440 0
Baseline (Week 0) and Follow-Up 1 (Week 9)
Secondary outcome [12] 402441 0
Complications (e.g. rate of graft-versus host disease) using data linkage to medical records
Timepoint [12] 402441 0
Assessed weekly through the trial period and up to 12 months
Secondary outcome [13] 402442 0
Healthcare utilisation will be assessed as a composite outcome (GP visits, ambulance call-outs, emergency department visits, hospital admissions, hospital length of stay, hospital re-admissions and re-admission length of stay, personal care and domestic support). These data will be obtained using a specific questionnaire developed by the health economist as well as accessing hospital medical records.
Timepoint [13] 402442 0
Assessed at follow up 1 (week 9), Follow-Up 2 (6 months) and Follow-Up 3 (12 months)
Secondary outcome [14] 402443 0
The intervention being studied is supportive care comprising physiotherapy, nutrition and behaviour change (psychology). A large body of high-quality evidence demonstrates that exercise is safe for people with cancer prior to, during and following treatment, including those with bony metastatic disease. Safety (adverse events) will be recorded and severity of events as per the Common Terminology Criteria for Adverse Events (CTCAE). Serious adverse events are those that are life threatening, result in hospital admission or prolongation or disability. Non-serious adverse events may include temporary muscular soreness, a normal response to exercise. A trial specific document will be used to record adverse events.
Safety criteria for starting, stopping and modifying exercise will be defined for all sites using a trial specific document.
Safety endpoints will be assessed by the number of adverse events related to the intervention and outcome assessments. The absence of serious adverse trial-related events will be used to indicate safety of the trial protocol.
Timepoint [14] 402443 0
Assessed at baseline (Week 0), weekly through the trial intervention period, follow up 1 (week 9), Follow-Up 2 (6 months) and Follow-Up 3 (12 months) after rehabilitation program
Secondary outcome [15] 402444 0
Survival
Timepoint [15] 402444 0
Assessed at follow up 1 (week 9), Follow-Up 2 (6 months) and Follow-Up 3 (12 months)
Secondary outcome [16] 402445 0
Patient acceptability survey designed for this study based upon Theoretical Framework of Acceptability
Timepoint [16] 402445 0
At the end of the intervention period -Follow up 1 (Week 9) after rehabilitation
Secondary outcome [17] 405129 0
Appendicular lean mass; measured by non-invasive bioimpedance spectroscopy
Timepoint [17] 405129 0
Baseline (Week 0), Follow-Up 1 (Week 9)
Secondary outcome [18] 405130 0
Phase angle; measured by non-invasive bioimpedance spectroscopy
Timepoint [18] 405130 0
Baseline (Week 0), Follow-Up 1 (Week 9)
Secondary outcome [19] 405133 0
Frailty using the Clinical Frailty Scale (CFS)
Timepoint [19] 405133 0
Baseline (Week 0), Follow-Up 1 (Week 9), and Follow-Up 3 (12 months)
Secondary outcome [20] 406470 0
Process evaluation: Fidelity of Training (provider level): will be assessed: using acceptability of the training to providers, measured through a 6-item questionnaire based on Theoretical Framework of Acceptability to deliver the intervention in accordance with Standard Operating Procedures (SOPs).
Timepoint [20] 406470 0
At the end of the intervention period -Follow up 1 (Week 9) after rehabilitation
Secondary outcome [21] 411894 0
Process evaluation: Fidelity of Delivery (provider level):
The number (%) of SOP-specified intervention components delivered to intervention participants, assessed by Specific trial developed Fidelity check list during the intervention, completed by providers after each session, this measurement strategy to be validated by analysing an audio-recording of two sessions per provider.
Timepoint [21] 411894 0
Completed after each session and assessed as percent meeting SOP guidelines at follow up 1 (week 9), after rehabilitation program
Secondary outcome [22] 411895 0
Process evaluation: Fidelity of Receipt (participant level): Number of sessions attended will be compared with number of sessions planned and on which modes (e.g., physical, nutritional) are offered.
Timepoint [22] 411895 0
Completed after each session and assessed as percent meeting SOP guidelines at follow up 1 (week 9), after rehabilitation program
Secondary outcome [23] 411974 0
Fidelity of Enactment (participant level): using Step count data; food diary compared with set goals.
Timepoint [23] 411974 0
assessed at follow up 1 (week 9), after rehabilitation program
Secondary outcome [24] 411975 0
Impact of prehabilitation, at the one site where this is a usual care intervention, will be assessed using tests of interaction of physical outcomes (functional exercise capacity using 6MWT, 30 sec sit to stand test), comparing these effects between a subgroup who received both interventions (prehabilitation and the trial rehabilitation) versus only one of the interventions.
Timepoint [24] 411975 0
Baseline (time point 0), follow up 1 (week 9)
Secondary outcome [25] 412208 0
Cancer related fatigue measured by the Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F).
Timepoint [25] 412208 0
Update Baseline (Week 0), Follow-Up 1 (Week 9), and Follow-Up 3 (12 months) after rehabilitation program
Secondary outcome [26] 412209 0
Process evaluation: A qualitative exploration of barriers and enablers to participant engagement will be conducted through tele-interviews with 20 trial participants (10 in the intervention arm; 10 in the control arm). After 10 participants (total) have been recruited, a random number table will be generated (from participant 10 to ~50) to determine which participants will be randomly sampled. Interview guides will be based on the Theoretical Domains Framework of behaviour change
Timepoint [26] 412209 0
Update at the follow-up assessment (i.e. 9 weeks) after rehabilitation program
Secondary outcome [27] 412210 0
Global score of health related quality of life using EORTC QLC-C30
Timepoint [27] 412210 0
Baseline (Week 0), Follow-Up 1 (Week 9), Follow up (6months) and Follow-Up 3 (12 months)

Eligibility
Key inclusion criteria
Patients who are 18 years or over, able to ambulate independently, are 30 days (+/-10 days) after an autologous or allogeneic BMT for haematological cancers, who are able to provide written informed consent and are proficient in English to understand exercise testing and training instructions as well as outcome assessments.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Concurrent, actively treated other malignancy or history of other malignancy treated within the past year, severe or unstable neurological, cardiorespiratory or musculoskeletal disease or mental illness that might compromise ability to perform exercise, unstable psychiatric or cognitive disorders, ECOG performance status >2.

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)
Randomisation will be implemented and concealed through the REDCap trial database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be generated by an independent statistician using permuted random blocks with stratification according to BMT type (allogeneic versus autologous). An independent database administrator will upload the randomisation schedule to REDCap.
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
stratification by BMT type allogeneic and autologous
allocated 1:1
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We plan to recruit 170 participants in total (85 participants per arm), giving us 80% power at 5% significance using conservative t-tests to detect a 10-point difference in the physical function scale of the EORTC-QLQ-C30, with a SD of 20 points. This allows for 25% loss to follow-up; a conservative estimate. The sample size calculation was based on detecting a small between-group effect size. According to Cocks et al the range of mean differences for a small effect size in the physical function domain is a score of 5-14 and we have chosen the mid-point of this range; 10. A pilot trial by Hung et al, conducted in a similar Australian population lends pilot data support to the choice of a between-group difference of 10 points for the EORTC QLQ-C30 physical functioning scale.

A Data and Safety Monitoring Board (DSMB) will be formed and will comprise of an independent biostatistician, a consumer and two independent cancer rehabilitation and clinical trial experts and meet twice yearly.

All analyses will follow intention-to-treat principles. The trial statistician will develop a full statistical analysis plan at trial commencement. Differences in mean change in baseline-to-9-week physical score between the intervention and usual care arms will be compared between the intervention and usual care arms using a mixed repeat measures ANOVA regression where trial arm, time and a trial arm-by-time interaction will be modelled as fixed effects, and site as a random effect. A McNemar chi squared (or exact equivalent) test will be used to analyse trial arm differences in binary outcomes post-baseline. Kaplan-Meier methods will be used to estimate survival curves with Cox proportional hazards regression models used for time-to-event analysis. An exploratory subgroup analysis of participants previously exposed to a usual care prehabilitation intervention at one centre will be undertaken. exploratory assessment of responders to rehabilitation using the 6MWT will also be undertaken. A test of interaction will be used to test for subgroup effects.

Three sub-studies will be conducted in parallel with the RCT to assess three process evaluation elements (fidelity; causal pathway; contextual influences):

An economic evaluation will be conducted from the health care perspective. Quality Adjusted Life Years (QALYs) will be calculated from the EORTC-QLQ-C30 responses reflecting Australian population norms. Cost-effectiveness comparing the cost and outcomes of the multidisciplinary intervention compared to standard care will be evaluated and incremental cost-effectiveness ratio (ICER) calculated as cost per QALY gained to justify the value of the intervention for national implementation studies that will follow. Extensive sensitivity analyses will be conducted to capture uncertainty around the ICER.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/08/2022
Actual
1/12/2022
Date of last participant enrolment
Anticipated
28/02/2025
Actual
Date of last data collection
Anticipated
28/02/2026
Actual
Sample size
Target
170
Accrual to date
90
Final
Recruitment in Australia
Recruitment state(s)
WA,VIC
Recruitment hospital [1] 21517 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 22829 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 22830 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 36424 0
3000 - Melbourne
Recruitment postcode(s) [2] 38118 0
3084 - Heidelberg
Recruitment postcode(s) [3] 38119 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 309983 0
Charities/Societies/Foundations
Name [1] 309983 0
World Cancer Research Fund (WCRF)
Country [1] 309983 0
United Kingdom
Primary sponsor type
University
Name
University of Melbourne
Address
Parkville VIC 3010
Country
Australia
Secondary sponsor category [1] 311784 0
None
Name [1] 311784 0
None
Address [1] 311784 0
None
Country [1] 311784 0
Other collaborator category [1] 282134 0
University
Name [1] 282134 0
Curtin University
Address [1] 282134 0
Kent St, Bentley WA 6102
Country [1] 282134 0
Australia
Other collaborator category [2] 282135 0
University
Name [2] 282135 0
Deakin University
Address [2] 282135 0
221 Burwood Highway, Burwood, Victoria 3125
Country [2] 282135 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309692 0
Peter MacCallum Cancer Centre HREC
Ethics committee address [1] 309692 0
Ethics committee country [1] 309692 0
Australia
Date submitted for ethics approval [1] 309692 0
11/02/2022
Approval date [1] 309692 0
17/06/2022
Ethics approval number [1] 309692 0
HREC/80768/PMCC 22/22

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

Contacts
Principal investigator
Name 115058 0
Prof Linda Denehy
Address 115058 0
University of Melbourne
Department of Physiotherapy
Alan Gilbert Building
Parkville VIC 3010
Country 115058 0
Australia
Phone 115058 0
+61383446428
Fax 115058 0
Email 115058 0
[email protected]
Contact person for public queries
Name 115059 0
Linda Denehy
Address 115059 0
University of Melbourne
Department of Physiotherapy
Alan Gilbert Building
Parkville VIC 3010
Country 115059 0
Australia
Phone 115059 0
+61383446428
Fax 115059 0
Email 115059 0
[email protected]
Contact person for scientific queries
Name 115060 0
Linda Denehy
Address 115060 0
University of Melbourne
Department of Physiotherapy
Alan Gilbert Building
Parkville VIC 3010
Country 115060 0
Australia
Phone 115060 0
+61383446428
Fax 115060 0
Email 115060 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?
Individual participant data will be retained and shared. De-identified data will be available to selected trial researchers along with a separate password-protected dataset linking trial identifiers to trial participants. Anonymised individual participant data that underlie the results reported in publications, will be stored in a secure online repository.
When will data be available (start and end dates)?
Beginning 12 months following publication with no end date.
Available to whom?
Determined by the Chief Investigator on a case by case basis
Available for what types of analyses?
Only to achieve the aims in the approved proposal
How or where can data be obtained?
Proposals should be directed to the Chief Investigator – Professor Linda Denehy ([email protected]) for approval


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
No additional documents have been identified.