A phase II randomized controlled trial of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy

Shabbir M H Alibhai, Daniel Santa Mina, Paul Ritvo, George Tomlinson, Catherine Sabiston, Murray Krahn, Sara Durbano, Andrew Matthew, Padraig Warde, Meagan O'Neill, Narhari Timilshina, Roanne Segal, Nicole Culos-Reed, Shabbir M H Alibhai, Daniel Santa Mina, Paul Ritvo, George Tomlinson, Catherine Sabiston, Murray Krahn, Sara Durbano, Andrew Matthew, Padraig Warde, Meagan O'Neill, Narhari Timilshina, Roanne Segal, Nicole Culos-Reed

Abstract

Background: Existing evidence demonstrates that 1:1 personal training (PT) improves many adverse effects of androgen deprivation therapy (ADT). Whether less resource-intensive exercise delivery models are as effective remains to be established. We determined the feasibility of conducting a multi-center non-inferiority randomized controlled trial comparing PT with supervised group (GROUP) and home-based (HOME) exercise programs, and obtained preliminary efficacy estimates for GROUP and HOME compared to PT on quality of life (QOL) and physical fitness.

Methods: Men with prostate cancer on ADT were recruited from one of two experienced Canadian centres and randomized 1:1:1 to PT, GROUP, or HOME. Randomization was stratified by length of ADT use and site. Participants completed moderate intensity aerobic and resistance exercises 4-5 days per week for 6 months with a target 150 min per week of exercise. Exercise prescriptions were individualized and progressed throughout the trial. Feasibility endpoints included recruitment, retention, adherence, and participant satisfaction. The efficacy endpoints QOL, fatigue, and fitness (VO2 peak, grip strength, and timed chair stands) in GROUP and HOME were compared for non-inferiority to PT. Descriptive analyses were used for feasibility endpoints. Between-group differences for efficacy endpoints were examined using Bayesian linear mixed effects models.

Results: Fifty-nine participants (mean age 69.9 years) were enrolled. The recruitment rate was 25.4% and recruitment was slower than projected. Retention was 71.2%. Exercise adherence as measured through attendance was high for supervised sessions but under 50% by self-report and accelerometry. Satisfaction was high and there was no difference in this measure between all three groups. Between-group differences (comparing both GROUP and HOME to PT) were smaller than the minimum clinically important difference on most measures of QOL, fatigue, and fitness. However, two of six outcomes for GROUP and four of six outcomes for HOME had a > 20% probability of being inferior for GROUP.

Conclusions: Feasibility endpoints were generally met. Both GROUP and HOME interventions in men with PC on ADT appeared to be similar to PT for multiple efficacy outcomes, although conclusions are limited by a small sample size and cost considerations have not been incorporated. Efforts need to be targeted to improving recruitment and adherence. A larger trial is warranted.

Trial registration: ClinicalTrials.gov: NCT02046837 . Date of registration: January 20, 2014.

Keywords: Androgen deprivation therapy; Cost-effectiveness; Exercise; Fatigue; Patient adherence; Physical fitness; Prostate cancer; Quality of life; Randomized controlled trial.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Research Ethics Board of University Health Network (REB #: 13–6629-CE) and the University of Calgary (HREBA.CC-17-0404). All participants provided written informed consent.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
This shows the flow of patients throughout the study following CONSORT guidelines
Fig. 2
Fig. 2
This shows the probability of inferiority of group-based (horizontal axis) and home-based (vertical axis) arms compared to the personal training arm for each of six outcomes (FACT-General (Panel a), FACT-Prostate (Panel b), FACT-Fatigue (Panel c), VO2 peak (Panel d), Sit-to-Stand (Panel e), Grip Strength (Panel f)) . The ellipse shows the 95% credible interval around the estimated effect. The light purple shaded areas represent inferiority regions that are larger than the minimum specified inferiority boundary for the specific outcome for one arm (either group-based or home-based), whereas the dark purple shaded areas represent inferiority regions where both arms are inferior to the personal training arm. See text and supplemental methods for more details

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