Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000256875
Ethics application status
Approved
Date submitted
14/01/2021
Date registered
10/03/2021
Date last updated
10/03/2021
Date data sharing statement initially provided
10/03/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Inflammation and the Microbiome: the effect of Physical Activity in cancer Survivors (IMPACT Trial)
Scientific title
Inflammation and the Microbiome: the effect of Physical ACTivity in breast cancer Survivors (IMPACTS Trial)
Secondary ID [1] 302918 0
Nil known
Universal Trial Number (UTN)
U1111-1262-1094
Trial acronym
IMPACTS trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 319934 0
Inflammation 319935 0
Condition category
Condition code
Cancer 317872 317872 0 0
Breast
Inflammatory and Immune System 318512 318512 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Inflammation and the microbiome: The effect of Physical Activity. This Randomised controlled trial is designed to investigate the effect of individualised, home based physical activity on the composition and function of the gut microbiome and systemic inflammation in cancer survivors. After informed consent is obtained, participants undergo baseline testing. Both tester and participant are blinded to the assigned intervention arm at baseline testing. After baseline testing, participants are randomised into either the exercise arm or the control arm.
Exercise arm:
Participants randomised to the exercise arm undergo a 12-week, home based individualised exercise program which adheres to the recommended physical activity guidelines from the American College of Sports Medicine (ACSM) which are echoed by Exercise and Sports Science Australia (ESSA) and the Clinical Oncology Society of Australia (COSA). This includes 150 minutes of moderate intensity aerobic physical activity (brisk walk, jog, cycle, swim) and 2-3 moderate intensity resistance exercise sessions per week. Participants in this study are given resistance bands of three different intensities to use at home to complete resistance exercises and prescribed resistance band and body weight exercises. After baseline testing an individual exercise program is devised by an accredited exercise physiologist with over 5 years’ experience in working with cancer cohorts. Whilst individualised, the program will consist of aerobic capacity exercise and resistance exercises including a mix of upper and lower body exercises. Participants will be educated on the use of the Rating of Perceived Exertion (RPE) scale to assess and monitor intensity of exercise. Participants will be given an activity diary to record their weekly physical activity including duration and intensity of aerobic capacity activity, step count and frequency of resistance exercises as well as load (which thera-band used), sets, repetitions and perceived intensity (RPE). There is no minimum duration for resistance exercise sessions, but participants will be prescribed a minimum of 6 exercises and a maximum of 8 exercises to complete per session. Weekly telephone support will be provided to participants in the exercise arm by researchers which will include a discussion around adherence and compliance to the exercise program, as well as discussion of any barriers faced by the participants. It is anticipated that the duration of these weekly phone calls will be 10-20 minutes in duration. This weekly telephone support will also be used to discuss intensity of the exercises and to plan and encourage exercise progression where appropriate.
Exercise progression:
Participants will be asked to use the modified RPE scale (1-10; 1= no exertion at all; 10 maximal exertion). They will be asked to rate the exercise at completion. The target RPE will be 4-6 indicating a moderate to hard intensity. Participants will be guided on the use of this scale at the initial testing session and educated on how to progress based on the scale. Once the exercise is rated 3-4 the participant will be encouraged to increase the reps/ sets or load as appropriate. Exercises will start at 2-3 sets of 8-10 reps and be progressed to 4 sets of 12 reps before increasing the load. Importantly, participants will be asked to perform exercises at approximately 4-6 RPE and progress the exercises when the perceived exertion falls below this rating.
Intervention code [1] 319203 0
Rehabilitation
Intervention code [2] 319204 0
Lifestyle
Intervention code [3] 319205 0
Behaviour
Comparator / control treatment
Control arm:
Participants randomised to the control arm after baseline testing are asked to maintain their current physical activity levels throughout the 12-week intervention. They will also be given an activity tracker to wear throughout the intervention to record physical activity levels. No telephone support will be provided to the control participants throughout the intervention. At the completion of the intervention, after follow-up testing, the control participants will be offered an opportunity to receive an individualised exercise program.
Control group
Active

Outcomes
Primary outcome [1] 326011 0
Fecal Microbiota profile assessed through 16s rRNA gene sequencing of fecal samples.
Timepoint [1] 326011 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Primary outcome [2] 326012 0
Systemic cytokine profile will be assessed through serum based immunoassay.
Timepoint [2] 326012 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [1] 389851 0
Quality of life- EORTC QLQ-C30 + BR23
Timepoint [1] 389851 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [2] 389852 0
Body composition - DXA scan. Outcomes of interest will be total body fat percentage, absolute body fat, absolute lean mass and visceral adiposity.
Timepoint [2] 389852 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [3] 389853 0
Barriers to exercise using the Exercise benefits barriers scale.
Timepoint [3] 389853 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [4] 389854 0
Self-reported physical activity levels using the International Physical activity questionnaire (IPAQ).
Timepoint [4] 389854 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [5] 389855 0
Pressure pain threshold testing - Algometry
Timepoint [5] 389855 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [6] 389856 0
General health questionnaire SF-36 to assess patients general health status.
Timepoint [6] 389856 0
Pre intervention- baseline and post intervention follow-up. Follow up testing will be performed within one week of completion of the 12-week intervention.
Secondary outcome [7] 390502 0
Objective physical activity monitoring through commercial activity tracker 'Misfit' device.
Timepoint [7] 390502 0
Assessed continuously throughout intervention.

Eligibility
Key inclusion criteria
Stage I-III breast cancer survivors who are 3-12 months post completion of their adjuvant treatment (hormone therapy and Herceptin may be continuing); Undergone curative surgery and/or chemotherapy and/or radiotherapy; Currently completing less than the recommended physical activity guidelines.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Metastatic disease; physical injuries which may preclude them from exercise; unmanaged cardiovascular or metabolic disease; inability to understand the participant information sheet and consent form or to give informed consent. Currently on anti-inflammatory medications that they cannot cease for the duration of the study; current or previous antibiotic use (in the past 3-months).

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)
Allocation to study groups is concealed from both researcher and participant until after baseline testing. Randomisation sequence was generated by an independent party and concealed in opaque envelopes prior to the beginning of the study. The opaque envelopes are numbered 1-60 and will be opened in numerical order.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
sequence was randomly generated using excel. groups were block randomised (in blocks of 10) to ensure equal distribution of participants per group.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A combination of statistical methods will be used in this study. Principle component analyses and distance based linear models will be used to integrate the microbiota data, metabolomics data and clinical data. Parametric and non-parametric multivariate analyses such as MANOVA will be used to assess changes in outcomes before and after the intervention.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/10/2019
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
31/03/2022
Actual
Sample size
Target
60
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 18204 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 18205 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 18206 0
St George Hospital - Kogarah
Recruitment hospital [4] 18207 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [5] 18208 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 32263 0
2031 - Randwick
Recruitment postcode(s) [2] 32264 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 32265 0
2217 - Kogarah
Recruitment postcode(s) [4] 32266 0
2560 - Campbelltown
Recruitment postcode(s) [5] 32267 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 307337 0
University
Name [1] 307337 0
University of New South Wales
Country [1] 307337 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW, High St, Randwick, NSW, Australia, 2052
Country
Australia
Secondary sponsor category [1] 307977 0
Hospital
Name [1] 307977 0
Prince of Wales Hospital
Address [1] 307977 0
320-346 Barker St, Randwick, NSW, Australia, 2031
Country [1] 307977 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307426 0
South Eastern Sydney Local Health District, Human Research Ethics Committee
Ethics committee address [1] 307426 0
Barker St, Randwick NSW 2031
Ethics committee country [1] 307426 0
Australia
Date submitted for ethics approval [1] 307426 0
01/04/2017
Approval date [1] 307426 0
31/05/2017
Ethics approval number [1] 307426 0
HREC 17/079

Summary
Brief summary
This study aims to determine whether a personalised exercise program has any protective effects on the gut microbiota in breast cancer survivors, which may have follow-on effects for overall health and immune response in these patients.

Who is it for?
You may be eligible for this study if you are aged between 18-80, you are a Stage I-III breast cancer survivor who is 3-12 months post completion of your adjuvant treatment (hormone therapy and Herceptin may be continuing), you have undergone curative surgery and/or chemotherapy and/or radiotherapy and you are currently completing less than the recommended physical activity guidelines (150 minutes of moderate intensity structured activity per week).

Study details
Participants who enroll in this study will be randomly allocated by chance (similar to flipping a coin) to either the intervention or the control treatment. Participants allocated to the intervention treatment will be prescribed an individualised exercise program to be completed for 12 weeks. The exercise program will involve a combination of aerobic exercise (such as jogging/swimming/cycling) and upper and lower limb resistance exercises using a thera-band. Each week, participants in the intervention group will also receive a 10–20-minute telephone call with a member of the research team to discuss their progress and any concerns they may have about the exercise program.

Participants allocated to the control treatment will be asked to maintain their current physical activity levels throughout the 12-week intervention. No telephone support will be provided to the control participants throughout the intervention. At the completion of the intervention, after follow-up testing, the control participants will be offered an opportunity to receive an individualised exercise program.

All participants in this study will undergo a baseline (pre-intervention) and follow-up assessment to determine their fitness levels, and will be asked to provide stool and blood samples to determine their levels of inflammation and the characteristics of their gut microbiome. All participants will be asked to wear an activity tracker to monitor their physical activity daily for the 12 weeks of the study.

It is hoped this research will demonstrate that moderate physical exercise has a positive effect on the gut microbiota of cancer survivors and this may also reduce systemic inflammation in these patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107202 0
Prof David Goldstein
Address 107202 0
Wallace Wurth Building, Cnr High and Botany St, Kensington, UNSW, Sydney, 2052
Country 107202 0
Australia
Phone 107202 0
+61 402035933
Fax 107202 0
Email 107202 0
[email protected]
Contact person for public queries
Name 107203 0
Dr Briana Clifford
Address 107203 0
Wallace Wurth Building, Cnr High and Botany St, Kensington, UNSW, Sydney, 2052
Country 107203 0
Australia
Phone 107203 0
+61 290651813
Fax 107203 0
Email 107203 0
[email protected]
Contact person for scientific queries
Name 107204 0
Dr Briana Clifford
Address 107204 0
Wallace Wurth Building, Cnr High and Botany St, Kensington, UNSW, Sydney, 2052
Country 107204 0
Australia
Phone 107204 0
+61 290651813
Fax 107204 0
Email 107204 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
De-identified individual patient data will not be available for this trial.


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.