Exercise prehabilitation in colorectal cancer
| ISRCTN | ISRCTN18133394 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18133394 |
| IRAS number | 321484 |
| Secondary identifying numbers | CPMS 23005, IRAS 321484 |
- Submission date
- 14/02/2023
- Registration date
- 17/02/2023
- Last edited
- 09/10/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Colorectal (bowel) cancer is the fourth most common cancer in the UK with over 40,000 cases diagnosed each year. About two in three people who are diagnosed with colorectal cancer have surgery as part of their treatment. Cancer treatment is good at extending the length of a person’s life, but many people are left more limited in their physical function when compared with similar people who have not had cancer or surgery. One way to try and combat this is with ‘prehabilitation’, which is the improvement of background levels of fitness amongst other things, before surgery. Given this, researchers want to study the effects of exercise on people before surgery for colorectal cancer and to work towards understanding why exercise can affect fitness levels amongst other things.
Who can participate?
Patients aged 18 years or older with colorectal cancer and a plan for curative surgery
What does the study involve?
Participants are randomly allocated to Prehabilitation with High-Intensity Interval Training (HIIT) only or to Prehabilitation with High-Intensity Interval Training (HIIT) and Resistance Exercise Training (RET) (ReHIIT). The study involves exercising for 8-12 sessions before surgery and three assessment sessions where participants will undergo tests of their physical function, blood and urine samples, an x-ray and ultrasound scan, testing of their nerves and muscles (EMG), a thigh biopsy, some questionnaires, and lung tests. In addition, they will also take saliva samples each week, wear a small device to track their function and record what they eat at four points during the study. The study takes about 10 weeks.
What are the possible benefits and risks of participating?
The primary aim of this study is not to directly benefit to participants in its design, but it is likely there may be some advantageous effects for participants. Participants will undergo a supervised exercise training regime, which is likely to increase their levels of physical fitness which may help them in day-to-day activities, and in their return to normal activities after surgery. Participants in the past have expressed feelings of reward for participation in trials and pleasure in the potential to help future patients.
Where is the study run from?
The University of Nottingham Medical School at the Royal Derby Hospital (UK)
When is the study starting and how long is it expected to run for?
October 2022 to August 2026
Who is funding the study?
Medical Research Council (MRC) (UK)
Who is the main contact?
Prof. Bethan Phillips, beth.phillips@nottingham.ac.uk
Contact information
Principal Investigator
Academic Unit of Injury, Recovery & Inflammation Sciences
School of Medicine, University of Nottingham
Derby
D22 2DT
United Kingdom
| Phone | +44 (0)1332 724676 |
|---|---|
| beth.phillips@nottingham.ac.uk |
Scientific
Academic Unit of Injury, Recovery & Inflammation Sciences
School of Medicine, University of Nottingham
Derby
D22 2DT
United Kingdom
| Phone | +44 (0)1332724640 |
|---|---|
| joshua.wall@nhs.net |
Public
Academic Unit of Injury, Recovery & Inflammation Sciences
School of Medicine, University of Nottingham
Derby
D22 2DT
United Kingdom
| Phone | +44 (0)1332724640 |
|---|---|
| joshua.wall@nhs.net |
Study information
| Study design | Single-centre interventional randomized controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Home, Hospital, Laboratory, University/medical school/dental school |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A randomised controlled trial of pre-operative high-intensity interval training versus high-intensity interval training plus resistance exercise training in patients with colorectal cancer scheduled for surgery with curative intent: a study to establish mechanisms of adaption to advance optimisation and stratification |
| Study acronym | EPiC |
| Study objectives | Purpose: To determine and delineate the underlying biological features of colorectal cancer burden in relation to cardiorespiratory and skeletal muscle adaptation to both High-Intensity Interval Training (HIIT) and High-Intensity Interval Training (HIIT) and Resistance Exercise Training (RET) = ReHIIT. Primary Objective: In relation to individuals with colorectal cancer scheduled for treatment with curative intent allocated to either HIIT or ReHIIT study arms: 1. To compare the composite change in anaerobic threshold and whole-body muscle mass Secondary Objectives: 1. To compare changes in each of cardiorespiratory and skeletal muscle function with HIIT vs ReHIIT 2. To determine the effects of HIIT vs ReHIIT on biological markers of post-operative recovery 3. To determine the relationship between biological features of colorectal cancer and exercise adaptation, and probable prognostic markers of responses to prehabilitation 4. To determine the effects of HIIT vs ReHIIT on clinical outcomes postoperatively |
| Ethics approval(s) | Approved 19/04/2023, South Central - Oxford C Research Ethics Committee (Health Research Authority (Bristol), Ground Floor, Temple Quay House, 2 The Square, BS1 6PN, UK; +44 (0)207 104 8241; oxfordc.rec@hra.nhs.uk), ref: 23/SC/0115 |
| Health condition(s) or problem(s) studied | Prehabilitation in patients with colorectal cancer scheduled for surgery with curative intent |
| Intervention | Patients attend a testing session to assess their physical function and measure muscle mass and structure using whole-body x-ray and ultrasound. Patients will be asked to complete simple questionnaires about their physical activity, diet and quality of life (QoL). Participants will be randomized using https://www.sealedenvelope.com. Participants will be stratified by sex and age group (5-year divisions). No blinding given the nature of the intervention. Study arms: 1. Prehabilitation with High-Intensity Interval Training (HIIT) only 2. Prehabilitation with High-Intensity Interval Training (HIIT) and Resistance Exercise Training (RET) = ReHIIT Patients will then complete 8-12 supervised sessions of exercise before surgery. The researchers will repeat the tests in the days before surgery, and again 6 weeks later. |
| Intervention type | Behavioural |
| Primary outcome measure | A composite primary endpoint of change in anaerobic threshold determined via cardiopulmonary exercise testing (CPET) (Hedges g effect size: 1.32) and whole-body muscle mass measured by dual-energy X-ray absorptiometry (DXA) (Hedges g effect size: 1.1) measured at baseline, pre-op (approx. 4 weeks after baseline) and 6 weeks post-op (approx. 10 weeks after baseline) |
| Secondary outcome measures | All outcome measures except those detailed otherwise will be measured at baseline, pre-op (approx. 4 weeks after baseline) and 6 weeks post-op (approx. 10 weeks after baseline): 1. Muscle protein synthesis determined via laboratory analysis of vastus lateralis muscle and saliva collection in conjunction with consumption of D2O 2. Muscle protein breakdown determined via blood sample analysis and 3-methylhistidine tracer consumption 3. Whole-body contractile mass determined via urine sample analysis and D3-creatine tracer consumption 4. VO₂ peak determined via CPET 5. VL muscle architecture determined via muscle ultrasound 6. Neuromuscular function determined via electromyography 7. Mitochondrial respiration determined via Oroboros analysis of vastus lateralis biopsies 8. Anabolic cell signalling determined via Western blotting analysis of vastus lateralis biopsies 9. Clinical outcomes determined via hospital data at the end of the study (approx. 10 weeks), or earlier if information becomes available 10. Dietary intake determined by analysis of a 4-day diet diary undertaken at four timepoints: prior to the first assessment (baseline assessment), during the intervention period (week 0-4), immediately post-operation (approx. week 4-5), and 3 weeks after the operation (approx. week 7-8) 11. Functionality (including physical activity) determined via a 6-minute walk test, handgrip strength, a short performance physical battery test (measuring balance, chair-rise ability and natural gait speed), a vertical jump test (using a G-Walk [Gait and Motion Technology Ltd, Bury St Edmunds] device), exercise assessments, Duke Activity Status Questionnaire, and leg-extensions measured via dynamometery 12. Habitual activity determined using a wearable device (ActivPAL™ monitor) at four timepoints: prior to the first assessment (baseline assessment), during the intervention period (week 0-4), immediately post-operation (approx. week 4-5), and 3 weeks after the operation (approx. week 7-8) 13. Self-reported QoL determined using the EORTC-QLQ-C30 questionnaire |
| Overall study start date | 01/10/2022 |
| Completion date | 01/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 56 |
| Key inclusion criteria | 1. Age ≥18 years at the time of discussion at the multidisciplinary team 2. No maximum age range so long as the participant is deemed fit for surgery by the clinical team 3. MDT outcome of a tissue-proven, or radiologically and clinically suspected colorectal neoplasia or dysplasia with the intention to treat with curative surgery 4. Due to undergo elective operative resection (by any route) with curative intent 5. Ability to and willingness to participate in exercise regimes and assessments 6. Able to travel to the Royal Derby Hospital for the duration of the study to facilitate exercise sessions 7. Availability for the study period to attend a minimum of eight exercise sessions and three assessment sessions |
| Key exclusion criteria | 1. Age <18 years at the time of discussion at the multidisciplinary team 2. No maximum age range so long as the participant is deemed fit for surgery by the clinical team 3. MDT outcome of a tissue-proven, or radiologically and clinically suspected colorectal neoplasia or dysplasia with the intention to treat with curative surgery 4. Due to undergo elective operative resection (by any route) with curative intent 5. Ability to and willingness to participate in exercise regimes and assessments 6. Able to travel to the Royal Derby Hospital for the duration of the study to facilitate exercise sessions 7. Availability for the study period to attend a minimum of eight exercise sessions and three assessment sessions |
| Date of first enrolment | 28/07/2023 |
| Date of final enrolment | 30/04/2026 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Derby
DE22 3NE
United Kingdom
Uttoxeter
New Road
Derby
DE22 3DT
United Kingdom
Sponsor information
University/education
Research and Innovation
E-floor, Yang Fujia Building
Jubilee Campus
Wollaton Road
Nottingham
NG8 1BB
England
United Kingdom
| Phone | +44 (0)115 7486731 |
|---|---|
| sponsor@nottingham.ac.uk | |
| Website | http://www.nottingham.ac.uk/ |
"ROR" |
https://ror.org/01ee9ar58 |
Funders
Funder type
Research council
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. Peer-reviewed scientific journals 2. Internal report 3. Doctoral thesis 4. Conference presentation 5. Publication on website |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 20/09/2023 | No | No |
Editorial Notes
09/10/2024: The scientific/public contact confirmed that the study was ongoing with no updates required.
20/09/2023: A link to the HRA research summary was added.
15/08/2023: Internal review.
04/08/2023: The recruitment start date has been changed from 12/07/2023 to 28/07/2023.
05/07/2023: The recruitment start date has been changed from 03/07/2023 to 12/07/2023.
26/06/2023: The recruitment start date has been changed from 15/05/2023 to 03/07/2023.
25/04/2023: The recruitment start date has been changed from 17/04/2023 to 15/05/2023.
24/04/2023: Ethics approval details added.
03/04/2023: The recruitment start date has been changed from 01/04/2023 to 17/04/2023.
08/03/2023: The recruitment start date has been changed from 01/03/2023 to 01/04/2023.
17/02/2023: Internal review.
16/02/2023: Trial's existence confirmed by the Medical Research Council.
