Study protocol of the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial: a two-arm, two-centre randomized controlled trial

Jennifer Brunet, Meagan Barrett-Bernstein, Kendra Zadravec, Monica Taljaard, Nathalie LeVasseur, Amirrtha Srikanthan, Kelcey A Bland, Barbara Collins, Julia W Y Kam, Todd C Handy, Sherri Hayden, Christine Simmons, Andra M Smith, Naznin Virji-Babul, Kristin L Campbell, Jennifer Brunet, Meagan Barrett-Bernstein, Kendra Zadravec, Monica Taljaard, Nathalie LeVasseur, Amirrtha Srikanthan, Kelcey A Bland, Barbara Collins, Julia W Y Kam, Todd C Handy, Sherri Hayden, Christine Simmons, Andra M Smith, Naznin Virji-Babul, Kristin L Campbell

Abstract

Background: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC. Aerobic exercise is associated with improved cognitive functioning in healthy older adults and adults with cognitive impairments. Accordingly, it holds promise as an intervention to prevent and/or manage CRCC. However, evidence from randomized controlled trials (RCTs) supporting a beneficial effect of aerobic exercise on CRCC is limited. The primary aim of the ACTIVATE trial is to evaluate the impact of supervised aerobic exercise on CRCC in women receiving chemotherapy for breast cancer.

Methods: The ACTIVATE trial is a two-arm, two-centre RCT. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy are recruited from hospitals in Ottawa (Ontario) and Vancouver (British Columbia), Canada. Recruits are randomized to the intervention group (aerobic exercise during chemotherapy) or the wait-list control group (usual care during chemotherapy and aerobic exercise post-chemotherapy). The primary outcome is cognitive functioning as measured by a composite cognitive summary score (COGSUM) of several neuropsychological tests. Secondary outcomes are self-reported cognitive functioning, quality of life, and brain structure and functioning (measured by magnetic resonance imaging (MRI)/functional MRI and electroencephalography). Assessments take place pre-chemotherapy (pre-intervention), mid-way through chemotherapy (mid-intervention/mid-wait period), end of chemotherapy (post-intervention/post-wait period; primary endpoint), 16-weeks post-chemotherapy, and at 1-year post-baseline.

Discussion: Aerobic exercise is a promising intervention for preventing and/or managing CRCC and enhancing quality of life among women diagnosed with breast cancer. The ACTIVATE trial tests several novel hypotheses, including that aerobic exercise can prevent and/or mitigate CRCC and that this effect is mediated by the timing of intervention delivery (i.e., during versus post-chemotherapy). Findings may support prescribing exercise during (or post-) chemotherapy for breast cancer and elucidate the potential role of aerobic exercise as a management strategy for CRCC in women with early-stage breast cancer.

Trial registration: The trial was registered with the ClinicalTrials.gov database ( NCT03277898 ) on September 11, 2017.

Keywords: Aerobic exercise; Breast neoplasm; Chemo-brain; Chemotherapy-related cognitive changes; Randomized controlled trial.

Conflict of interest statement

The authors declare that they have no financial or non-financial competing interests.

Figures

Fig. 1
Fig. 1
SPIRIT flow diagram for the schedule of enrollment, interventions, and assessments for the ACTIVATE trial
Fig. 2
Fig. 2
The ACTIVATE trial design

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