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Trial registered on ANZCTR


Registration number
ACTRN12614000317695
Ethics application status
Approved
Date submitted
18/03/2014
Date registered
25/03/2014
Date last updated
21/11/2018
Date data sharing statement initially provided
21/11/2018
Date results information initially provided
21/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The efficacy of exercise training and nutritional supplementation in prostate cancer survivors
Scientific title
The efficacy of resistance exercise training and nutritional supplementation of calcium, vitamin D and protein on musculoskeletal health, cardiometabolic risk factors and health-related quality of life in prostate cancer survivors treated with androgen deprivation therapy when compared to usual care
Secondary ID [1] 282668 0
Nil known
Universal Trial Number (UTN)
Trial acronym
IMPACT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer survivors treated with androgen deprivation therapy 289366 0
Condition category
Condition code
Cancer 291540 291540 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomised controlled trial in which participants treated with androgen deprivation therapy for prostate cancer will participant in progressive resistance exercise training program and daily supplementation of calcium, vitamin D and protein for 52 weeks. The exercise training program will be individually tailored and follow the key training principles of specificity, progressive overload and periodisation. Participants will attend two gym-based training sessions per week and complete one home-based training session. For the first 26 weeks, both gym-based training sessions will be supervised by a student exercise physiologist supervised by an accredited exercise physiologist. After 26 weeks, only one gym-based training session will be supervised and the participant will be instructed to perform the other gym-based session unsupervised. Each session will last approximately 60 minutes. Participants will perform resistance, weight-bearing impact and functional exercises. Participants will perform resistance exercises in two sets of 8-15 repetitions at a weight that cannot be lifted more than 8-15 times. Participants will perform weight-bearing impact exercises in three sets of 10-20 repetitions. Participants will perform functional exercises for 30-60 seconds or until fatigue. To enhance benefits from the exercise training program, participants will also consume a nutritional supplement of approximately 500-600mg calcium, 2000IU vitamin D and 20-25g protein daily. The supplement will be administered via a combination of a powder based supplement (mixed with water) and oral capsule.

Compliance with the gym-based exercise training program will be assessed via the training notes kept by the participant's trainer. Compliance with the home-based exercise training program will be assessed via an exercise diary (which will be regularly assessed by the participant's trainer). Compliance with the supplement will be assessed via a supplement compliance calendar (which will be regularly assessed by the participant's trainer and/or other researchers). Additionally, all non-consumed supplements will be returned to the researchers and compliance will assessed to ensure it matches the compliance calendar.
Intervention code [1] 288815 0
Lifestyle
Intervention code [2] 289028 0
Rehabilitation
Comparator / control treatment
Participants randomised into this control group will receive usual care for men treated with ADT. Usual care for these men does not include additional access to exercise training or nutritional supplementation and typically includes minimal advice regarding these areas.
Control group
Active

Outcomes
Primary outcome [1] 289797 0
Femoral neck areal bone mineral density (measured via DXA)
Timepoint [1] 289797 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [1] 306919 0
Total hip and lumbar spine areal bone mineral density (measured via DXA)
Timepoint [1] 306919 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [2] 306920 0
Total and regional body composition (lean mass, fat mass and percentage fat mass; measured via DXA)
Timepoint [2] 306920 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [3] 306921 0
Bone microarchitecture (radius 4%/66% and tibia 4%/66%; measured via pQCT)
Timepoint [3] 306921 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [4] 306922 0
Muscle and subcutaneous fat cross-sectional area (radius 66% and tibia 66%; measured via pQCT)
Timepoint [4] 306922 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [5] 306923 0
Basic anthropometric (height, weight, BMI, chest circumference, hip circumference, waist circumference)
Timepoint [5] 306923 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [6] 306924 0
Resting physiological (heart rate and blood pressure)
Timepoint [6] 306924 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [7] 306925 0
Blood markers (albumin, calcium, phosphorus, creatinine, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, high sensitivity C-reactive protein and glucose)
Timepoint [7] 306925 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [8] 306926 0
Health related quality of life (measured via FACT-F/Fact-P questionnaires)
Timepoint [8] 306926 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [9] 306927 0
Physical activity (measured via CHAMPS questionnaire)
Timepoint [9] 306927 0
Baseline, 26 weeks and 52 weeks.
Secondary outcome [10] 306928 0
Diet (measured via 24 hour food recall)
Timepoint [10] 306928 0
Baseline, 26 weeks and 52 weeks.

Eligibility
Key inclusion criteria
Men aged 50-85 years currently undergoing treatment for prostate cancer with androgen deprivation therapy. Treatment with androgen deprivation therapy must be planned to be continuous, pharmacological, administered for greater than three months at enrollment and expected to be administered for the duration of the intervention (52 weeks). All participants in the study must also have received approval from their local physician to participate in the study.
Minimum age
50 Years
Maximum age
85 Years
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: do not have the ability to complete surveys in the English language; any disorder known to affect bone, calcium or vitamin D metabolism (other than hypogonadism); currently receiving pharmacological intervention known to affect bone metabolism (other than androgen deprivation therapy); supplementation with protein, calcium (>600 mg/d) or vitamin D (>1000 IU/d) in the past three months; have undertaken progressive resistance training (>1 session/wk) or high impact weight bearing exercise (>150 min/wk) in the past three months; current smokers; weight greater than 159kg; have plans to travel for greater than six weeks continuously within the following 52 weeks; any absolute contraindications to exercise training according to the American College of Sports Medicine guidelines.

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)
Participants will be recruited via direct referral from clinicians across various hospitals, private practices and health networks in combination with promotion via PCa support groups and advertisements in state/local newspapers within Melbourne and surrounding areas in Victoria, Australia. The direct referral process will include mass mail outs to potential participants and face-to-face discussions during regular consultations with physicians/specialists. PCa support groups will be initially contacted via email with information regarding the study, with an option to provide a brief presentation to groups interested. All potential participants will be screened initially via telephone to determine their eligibility based on the criteria outlined above. All eligible participants will be required to obtain medical approval from their physician and provide informed consent before participating in the study.

Randomisation will be at the level of the individual participant following baseline testing, stratified by age (<65 or =65 years) and body mass index (<30 or =30 kg/m2), using a computer-generated random number sequence by an independent researcher. Due to limited funding, neither the participants nor researchers involved in the testing will be blinded to the group allocation, with the exception of the DXA and pQCT scans which will be assessed independently.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be computer-generated (random number table) by an independent researcher.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size calculations are based on our previous research in healthy and ADT treated men. The mean (SD) annual loss in femoral neck, hip and spine BMD in ADT treated men was 3.0% (4.5), 2.6% (2.8) and 3.9% (3.0), respectively. Our previous exercise trials in healthy older men have shown that 12 months of training can increase spine aBMD by 1.5-2.0% (SD 2.9) and hip aBMD by 1.2-1.8% (SD 2.8). We estimate a conservative net difference in aBMD in favour of the intervention of ~3.5-4.0% at the hip and spine. Based on these estimates, 29 men in each group will provide 90% power (P<0.05, two-tailed) to detect a difference of this magnitude (assuming a SD of 4.0). A net benefit of this magnitude is clinically relevant as there is evidence that a 1-2% gain in aBMD translates into a 7-14% reduction in fracture risk. For pQCT bone measures, radius and tibia cortical area decreased by 11.5% (8.8) and 12.5% (7.4), respectively over 12 months in ADT treated men. While few long-term trials have examined the effect of exercise training on pQCT bone geometry in older men, several intervention trials in older adults have shown that a targeted weight-bearing impact exercise program can have beneficial effects on cortical bone. Assuming that the proposed intervention can half the rate of loss in cortical area, we estimate that we will require 39 men per group (SD 8.0; 90% power, two-tailed, P<0.05). Based on a previous study and a meta-analysis showing that ADT is associated with an average 7.7% gain in fat and a 2.8% loss in lean mass over 3-12 months, and that exercise training can prevent the gain in FM and increase (1-5%) or preserve LBM relative to usual care in men on ADT, we estimate a sample size of 24-32 in each group will be required to observe a preservation in LBM and FM in the intervention group vs. usual care (90% power, two-tailed, P<0.05). Assuming a conservatively projected 30% drop-out, an estimated sample size of 51 men per group (102 in total) will be required. Based on previous studies in ADT treated men focusing on a number of our secondary outcomes, we estimate that we will have sufficient power (80-90%, P<0.05, two-tailed) to detect the following intervention effects: 20-40% for muscle strength; 8-22% for muscle function; 4 points for fatigue (FACT-F), 15% for fasting plasma glucose and 14% for serum IL-6 and 20% for CRP. We will also have sufficient sample to detect a clinically meaningful difference of 0.5 SD in the AQoL-8D and 9 points on FACT-P (disease specific QoL).

Primary analyses will be conducted on an intention-to-treat basis using STATA statistical software (STATA, College Station, TX, USA). Per protocol analysis will also be performed by including all participants who are at least 66% compliant to the exercise (two of three sessions per week) and 80% compliant to the supplements. Initially, descriptive statistics will be computed to compare the intervention and usual care groups on background variables and baseline measures. All data will be screened for outliers and the normality of the distribution of all data will be assessed using Kolmogorov-Smirnov tests, with skewed data log transformed prior to analysis. Linear mixed models with random effects will be used to evaluate the effects of the intervention compared to usual control. Potential covariates to be included will be: age, duration of ADT use, other chronic conditions, change in medication and change in habitual physical activity or diet. Where possible, we will obtain endpoint measures from all withdrawals and include all randomised subjects in the final analysis. For participants who are lost to follow- up, missing data will be handled with multiple imputation, with subsequent sensitivity analyses to evaluate the effect of potential non-random attrition. Baseline measures and changes in outcome variables will be presented as means ± SD or 95 % confidence intervals. A significance level of P<0.05 will be adopted for all statistical tests.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 12480 0
The Alfred - Prahran
Recruitment hospital [2] 12481 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 24801 0
3004 - Prahran
Recruitment postcode(s) [2] 24802 0
3000 - Melbourne

Funding & Sponsors
Funding source category [1] 288756 0
University
Name [1] 288756 0
Deakin University
Address [1] 288756 0
Deakin University, Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, 221 Burwood Highway, Victoria, 3125.
Country [1] 288756 0
Australia
Primary sponsor type
University
Name
Deakin University
Address
Deakin University, Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, 221 Burwood Highway, Victoria, 3125.
Country
Australia
Secondary sponsor category [1] 287452 0
Charities/Societies/Foundations
Name [1] 287452 0
YMCA Victoria
Address [1] 287452 0
582 Heidelberg Road
Fairfield, Victoria, 3078
Country [1] 287452 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290595 0
Deakin University Human Research Ethics Committee
Ethics committee address [1] 290595 0
Human Research Ethics
Deakin Research Integrity
Deakin University
221 Burwood Highway
Burwood, Victoria, 3125
Ethics committee country [1] 290595 0
Australia
Date submitted for ethics approval [1] 290595 0
Approval date [1] 290595 0
26/09/2013
Ethics approval number [1] 290595 0
2013-184
Ethics committee name [2] 295181 0
Alfred Hospital Ethics Committee
Ethics committee address [2] 295181 0
The Alfred, 55 Commercial Road, Melbourne, VIC 3004, Australia
Ethics committee country [2] 295181 0
Australia
Date submitted for ethics approval [2] 295181 0
22/10/2015
Approval date [2] 295181 0
12/01/2016
Ethics approval number [2] 295181 0
455/15
Ethics committee name [3] 301990 0
Peter MacCallum Cancer Centre Ethics Committee
Ethics committee address [3] 301990 0
Peter MacCallum Cancer Centre
305 Grattan Street
Melbourne VIC 3000
Ethics committee country [3] 301990 0
Australia
Date submitted for ethics approval [3] 301990 0
02/08/2017
Approval date [3] 301990 0
23/10/2017
Ethics approval number [3] 301990 0
SSA/17/PMCC/151

Summary
Brief summary
The aim of this study is to evaluate the efficacy of resistance exercise training and nutritional supplementation in prostate cancer survivors treated with androgen deprivation therapy.

Who is it for?
You may be eligible to join this study if you are a male aged 50-85 years and are currently undergoing treatment for prostate cancer with androgen deprivation therapy which is expected to continue for at least 52 weeks.

Study details
Participants in this study will be randomly (by chance) allocated to one of two groups. Participants in one group will participate in an individually tailored progressive resistance exercise training program three times a week and receive daily supplementation of calcium, vitamin D and protein over a period of 52 weeks. Participants in the other group will receive the usual care administered to men undergoing androgen deprivation therapy.

Participants will be assessed at baseline, 26 weeks and 52 weeks in order to determine any changes in musculoskeletal health, cardiometabolic risk factors, and health-related quality of life. Assessment is by bone scans, blood tests, and questionnaires. The results of this study may contribute to the development of exercise and nutritional guidelines for optimising overall health in men treated with androgen deprivation therapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 40738 0
Dr Steve Fraser
Address 40738 0
Deakin University, Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria, 3125
Country 40738 0
Australia
Phone 40738 0
+61392446012
Fax 40738 0
Email 40738 0
steve.fraser@deakin.edu.au
Contact person for public queries
Name 40739 0
Dr Steve Fraser
Address 40739 0
Deakin University, Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria, 3125
Country 40739 0
Australia
Phone 40739 0
+61392446012
Fax 40739 0
Email 40739 0
steve.fraser@deakin.edu.au
Contact person for scientific queries
Name 40740 0
Dr Steve Fraser
Address 40740 0
Deakin University, Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, 221 Burwood Highway, Burwood, Victoria, 3125
Country 40740 0
Australia
Phone 40740 0
+61392446012
Fax 40740 0
Email 40740 0
steve.fraser@deakin.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
The availability of the IPD is being discussed
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 358 0
Study protocol
Citation [1] 358 0
Link [1] 358 0
Email [1] 358 0
Other [1] 358 0
https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-017-2185-z

The study protocol has been published in Trials.
Attachment [1] 358 0
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary