Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001422213
Ethics application status
Approved
Date submitted
21/08/2018
Date registered
27/08/2018
Date last updated
11/02/2021
Date data sharing statement initially provided
30/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Exercise training for cancer survivors with chemotherapy-induced peripheral neuropathy
Scientific title
Exercise rehabilitation for cancer survivors with chemotherapy-induced peripheral neuropathy:
Impact and mechanisms
Secondary ID [1] 295862 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chemotherapy-induced peripheral neuropathy 309329 0
Condition category
Condition code
Cancer 308193 308193 0 0
Any cancer
Neurological 308234 308234 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Home and clinic exercise interventions will be delivered by exercise physiologists affiliated with exercise facilities at each site. Both exercise interventions will consist of three weekly one-hour sessions for 8-weeks. Our experience has indicated that an 8-week exercise program is sufficient to demonstrate intervention benefits while minimising patient attrition. Each one-hour session will be split between cardiovascular, resistance, balance training, and stretching exercises. This design of each session allows the exercise intervention to meet American Cancer Society and American College of Sports Medicine physical activity guidelines for cancer survivors, while also including balance training exercises with demonstrated benefit in smaller studies in a CIPN population. All cardiovascular, resistance, and balance training exercises will be tailored to individual fitness level using a rating of perceived exertion of 13-15/20 (high-moderate intensity exercise). Stretching exercises will be conducted at a more moderate rating of perceived exertion of 10-12/15. Rating of perceived exertion is the selected intensity metric because of its strong correlation to varied objective measures of exercise intensity across exercise modalities, facilitating simple and streamlined prescription and monitoring of intensity without need for equipment both in clinic and at home.

Cardiovascular exercise will be treadmill and outdoor walking or, if patient functional status dictates, stationary cycling in clinic. Resistance training will consist of two sets of 10-15 repetitions of four functional multi-joint movements in each session, two in the upper body and two in the lower body, using dumbbells, Therabands, or exercise machines as appropriate. Patients will be provided with Therabands to enable completion of resistance exercises at home. Balance training exercises will also consist of two sets of four exercises in each session, with two bipedal exercises ((semi-)tandem walking and/or stance)) and two exercises in unipedal stance. Unstable surfaces (i.e. foam mats, pillows) and controlled movements (i.e. torso rotation) will be added as necessary to increase difficulty of balance activities. Resistance and balance training exercise prescriptions will be split into a ‘Session A’ and ‘Session B’ featuring complementary exercises.

Patients will undergo a comprehensive evaluation of initial fitness by an exercise physiologist before beginning their clinic or home exercise program, including screening for a range of comorbidities according to established American College of Sports Medicine guidelines for cancer survivors; as part of this evaluation, a full medical history will be obtained from the medical record for each patient. Patients randomized to the control group and subsequent home intervention will receive a written prescription and demonstration of all home exercises (Session A and Session B) with the frequency, intensity (RPE), time (or number of sets/repetitions) and type of exercises noted and described. Modifications of all exercises to reduce and increase intensity will also be included in the prescription. Exercises will be modified as necessary to facilitate safe completion at home (i.e. tandem walking exercises only prescribed if patient has access to a clear walkway with a wall within arm’s reach). A designated space for patients to record the intensity, time, and type of each exercise performed at each home session will be provided in the form of a patient diary to monitor adherence and compliance to home exercise prescriptions. Follow-up phone calls from the prescribing exercise physiologist in weeks 2 and 5 will be used to monitor the progress of the home intervention, answer patient questions, and monitor the occurrence of any adverse events. Exercise physiologists will also be available to receive calls from patients throughout the duration of the intervention.

Clinic exercise sessions will be delivered in a 1-on-1 or small group format by exercise physiologists. A similar patient diary will be completed by exercise physiologists to monitor patient adherence, compliance and adverse events at clinic-based sessions. Home and clinic exercise diaries will also be used to monitor the fidelity of the prescribed exercises to the established intervention protocol. Additionally, diaries of home and clinic-based exercise sessions will be utilised to guide the progression of exercises throughout the intervention; RPE will be recorded for each exercise at all sessions, and a recorded RPE below 13 for an exercise will indicate a modification to that exercise to increase intensity (i.e. increased resistance for resistance training exercises; addition of unstable surface and/or upper body movement for balance training exercises; increased speed, incline or resistance for cardiovascular exercise). Modifications of exercise intensity will be guided by exercise physiologists in clinic and written exercise prescriptions at home. Phone calls from the prescribing exercise physiologist during home interventions will further assist with appropriate progression of exercise intensity.
Intervention code [1] 312199 0
Rehabilitation
Intervention code [2] 312227 0
Treatment: Other
Comparator / control treatment
The control treatment is 8-weeks without formal exercise intervention. The control group will be prescribed a home-based exercise intervention following the 8-week control period.
Control group
Active

Outcomes
Primary outcome [1] 307159 0
Total Neuropathy Score (clinical version)
Timepoint [1] 307159 0
Baseline, 8-week assessment (primary endpoint), 16-week assessment, 6-month follow up
Secondary outcome [1] 350933 0
Patient reported-neuropathy -- EORTC CIPN-20
Timepoint [1] 350933 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow-up
Secondary outcome [2] 350952 0
Quality of Life -- SF-36
Timepoint [2] 350952 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [3] 350953 0
CIPN Rasch Built Overall Disability Subscale (CIPN-R-ODS)
Timepoint [3] 350953 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [4] 350954 0
Incidental and Planned Activity Questionnaire (IPAQ)
Timepoint [4] 350954 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [5] 350955 0
Iconography Falls Efficacy Scale (ICON-FES)
Timepoint [5] 350955 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [6] 350956 0
Nerve conduction studies (sural & tibial)
Timepoint [6] 350956 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [7] 350957 0
Gait stability

Assessed while participants walk over unobstructed flat and uneven 20-m walkways at self-selected speed. Gait stability (harmonic ratios of accelerations in 3D) and variability (step time and swing time) will be computed from accelerations recorded in 3D by inertial sensors.
Timepoint [7] 350957 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [8] 350958 0
6-minute walk test

Assessed using a stopwatch on a measured 15 metre pathway
Timepoint [8] 350958 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [9] 350959 0
Timed up and go

Measured using stopwatch
Timepoint [9] 350959 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [10] 350960 0
Choice stepping test

Reaction time tests, quantified using validated purpose-built equipment and methodology developed at NeuRA
Timepoint [10] 350960 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [11] 350961 0
Swaymeter (standing balance)
Timepoint [11] 350961 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [12] 350962 0
Coordinated stability

Dynamic balance assessment, quantified using validated purpose-built equipment and methodology developed at NeuRA
Timepoint [12] 350962 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [13] 350963 0
Spatiotemporal gait analysis

Computed based on analyses of spatiotemporal parameters obtained from inertial sensors during the 6-minute walk test.
Timepoint [13] 350963 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up
Secondary outcome [14] 350964 0
Corneal confocal microscopy (small nerve fibre morphology)
Timepoint [14] 350964 0
Baseline, 8-week assessment, 16-week assessment, 6-month follow up

Eligibility
Key inclusion criteria
1. Grade 2 or 3 chemotherapy-induced peripheral neuropathy (symptoms affecting function)
2. At least 3 months post-neurotoxic cancer treatment
3. Previously treated with cancer treatments for which neuropathy is a known side effect
4. Greater than 18 years of age
5. Able to provide written informed consent
6. Cleared by a physician to participate in a structured exercise program
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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)
Allocation by contacting the off-site holder of the allocation schedule
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-based randomisation stratified by age (group 1: less than or equal to 60 years; group 2: greater than or equal to 60 years) and study centre.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Following the initial baseline assessment, patients will be randomised to two groups: an 8-week exercise intervention or usual care control group. After the initial 8-week period, the control group will receive an 8-week prescribed home exercise intervention during study weeks 9-16, allowing for a secondary analysis of the relative benefits of clinic vs. home-based intervention. The retention of benefits from both exercise delivery modalities will be evaluated through a 6-month follow up assessment.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Analyses will be conducted according to the intention-to-treat principle—patients will only be considered non-compliant in the event of withdrawal from the study for any reason. Patient demographic, treatment and clinical characteristics and study outcomes will be described within groups and overall using standard descriptive statistics. The primary outcome of mean TNS score at the 8-week assessment will be compared between randomised groups using a two-sample t-test. A further exploratory analysis will adjust for baseline TNS score. Other continuous outcomes will also be compared using t-tests. Chi-square tests will be used to compare categorical variables and analyse falls data. Regression analyses will be used to explore predictors of outcome and to perform adjusted analyses if applicable. Longitudinal outcomes measured more than once in the same participant will be analysed using methods such as generalised estimating equations that allow for the potential correlation between repeated observations in the same participant. All effects will be presented with 95% confidence intervals where possible.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/01/2019
Actual
18/03/2019
Date of last participant enrolment
Anticipated
30/06/2021
Actual
Date of last data collection
Anticipated
30/12/2021
Actual
Sample size
Target
96
Accrual to date
39
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 11701 0
Prince of Wales Hospital - Randwick
Recruitment hospital [2] 11702 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment hospital [3] 11703 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 23782 0
2031 - Randwick
Recruitment postcode(s) [2] 23783 0
2050 - Camperdown
Recruitment postcode(s) [3] 23784 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 300460 0
Other Collaborative groups
Name [1] 300460 0
Sydney Partnership for Health, Education, Research & Enterprise (SPHERE)
Country [1] 300460 0
Australia
Funding source category [2] 300467 0
Government body
Name [2] 300467 0
Cancer Institute NSW
Country [2] 300467 0
Australia
Funding source category [3] 303423 0
Charities/Societies/Foundations
Name [3] 303423 0
World Cancer Research Fund
Country [3] 303423 0
United Kingdom
Primary sponsor type
Individual
Name
Professor David Goldstein
Address
Lowy Cancer Research Centre
UNSW Sydney
Sydney NSW 2052
Country
Australia
Secondary sponsor category [1] 299929 0
Individual
Name [1] 299929 0
Dr Susanna Park
Address [1] 299929 0
Brain and Mind Centre
94 Mallett St
Camperdown NSW 2050
Country [1] 299929 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301263 0
South Eastern Sydney Local Health District
Ethics committee address [1] 301263 0
Human Research Ethics Committee
Room G71 East Wing
Edmund Blacket Building
Prince of Wales Hospital
Randwick, NSW 2031
Ethics committee country [1] 301263 0
Australia
Date submitted for ethics approval [1] 301263 0
31/08/2018
Approval date [1] 301263 0
09/11/2018
Ethics approval number [1] 301263 0
HREC Ref. # 18/192

Summary
Brief summary
The purpose of this study is determine whether exercise-based rehabilitation is effective in cancer survivors with Chemotherapy Induced Peripheral Neuropathy (CIPN).

Who is it for?

You may be eligible for this study if you are an adult with chemotherapy-induced peripheral neuropathy symptoms which persist after the completion of your chemotherapy treatment.

Study details

Participants in this study will be randomly sorted into two groups:
- Group 1: participates in 3 weekly exercise sessions for 8 weeks. These sessions will be held face to face and either one-one-one or in small groups. Exercises will be individualized based on your balance abilities and strength and fitness levels and include cardiovascular, resistance, balance and stretching exercises.
- Group 2: will receive an at-home exercise intervention after an 8 week delayed start. The home-exercises will also be completed 3 times a week for 8 weeks, be individualized, and include the same types of exercises as Group 1.
Participants will also be required to complete fitness, nerve, functional and questionnaire assessments before and after their 8-week exercise program.

It is hoped that this study will provide evidence regarding the effectiveness of exercise-based rehabilitation for people with chemotherapy induced peripheral neuropathy and establish the merits of home-based v clinic-based treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86410 0
Prof David Goldstein
Address 86410 0
Lowy Cancer Research Centre
UNSW Sydney
Sydney NSW 2052
Country 86410 0
Australia
Phone 86410 0
+61293828837
Fax 86410 0
Email 86410 0
d.goldstein@unsw.edu.au
Contact person for public queries
Name 86411 0
Prof David Goldstein
Address 86411 0
Lowy Cancer Research Centre
UNSW Sydney
Sydney NSW 2052
Country 86411 0
Australia
Phone 86411 0
+61293828837
Fax 86411 0
Email 86411 0
d.goldstein@unsw.edu.au
Contact person for scientific queries
Name 86412 0
Prof David Goldstein
Address 86412 0
Lowy Cancer Research Centre
UNSW Sydney
Sydney NSW 2052
Country 86412 0
Australia
Phone 86412 0
+61293828837
Fax 86412 0
Email 86412 0
d.goldstein@unsw.edu.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?
Individual participant data underlying published results only
When will data be available (start and end dates)?
Data will be available for 5 years from the date of publication of the study manuscript
Available to whom?
Case-by-case basis at the discretion of the Primary Sponsor
Available for what types of analyses?
To be determined by primary sponsor on case-by-case basis
How or where can data be obtained?
Through contact with the Principal Investigator (d.goldstein@unsw.edu.au)


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
SourceTitleYear of PublicationDOI
EmbaseEvidence of slow and variable choice-stepping reaction time in cancer survivors with chemotherapy-induced peripheral neuropathy.2021https://dx.doi.org/10.1016/j.gaitpost.2021.07.010
N.B. These documents automatically identified may not have been verified by the study sponsor.