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

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.

Changes in EEG microstate dynamics and cognition post-chemotherapy in people with breast cancer: A pilot study

“…The ACTIVATE trial included a wide range of outcome measures as described in Brunet et al 28,29 . From these measures, we selected 1 self-report measure and 1 objective neuropsychological measure collected at baseline (before chemotherapy) and following chemotherapy to broadly capture the symptoms of cognitive impairment the sample experienced.…”

“…We analyzed data collected during 2018-2020 as part of a longitudinal randomized controlled trial entitled Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) 28 , which focused on testing the effects of aerobic exercise on cognition function and quality of life. In the ACTIVATE trial, participants were randomized to complete supervised, progressive, aerobic exercise during chemotherapy (EX) or wait-list usual care control (DE); in the present study, all participants were collapsed into a single group.…”

“…In the ACTIVATE trial, participants were randomized to complete supervised, progressive, aerobic exercise during chemotherapy (EX) or wait-list usual care control (DE); in the present study, all participants were collapsed into a single group. See protocol for full details in Brunet et al 28,29 . EEG data collection was optional for participants.…”

Structural Neuroimaging Findings Related to Adult Non-CNS Cancer and Treatment: Review, Integration, and Implications for Treatment of Cognitive Dysfunction

“…To date, there are no established evidencebased treatments for CRCD, though preliminary studies have investigated numerous treatment modalities, including pharmacological and dietary interventions, behavioral therapies, cognitive training, aerobic and non-aerobic exercise, and acupuncture [5,[87][88][89][90][91][92][93][94][95][96][97]. Such clinical trials have primarily focused on cognition, mood, and/or quality of life outcomes; a small number of studies have recently begun to investigate the effects of treatments for CRCD on functional neuroimaging outcomes [98][99][100][101][102][103]. To date, only one study has examined structural changes as related to a CRCD intervention, illustrating some possible benefit for white matter integrity after acupuncture, though only three patients participated in the intervention and control groups [84].…”