Trial Outcomes & Findings for Adaptive Training Exercise Programs for Improving Cardiorespiratory Fitness After Breast Cancer Treatment, The ACTIVATE Trial (NCT NCT04667481)

Adaptive Training Exercise Programs for Improving Cardiorespiratory Fitness After Breast Cancer Treatment, The ACTIVATE Trial

Will be determined with all-cause intervention discontinuation rate, which is the proportion of all intervention participants who permanently stop the intervention prior to week 24 for any reason.

Intervention safety will be determined by reviewing and quantifying the number of adverse events (mild, moderate, or severe), serious adverse events, and by reviewing the type and severity of adverse events attributed to study procedures among each study group.

Study feasibility will be measured by calculating recruitment rates (proportion of enrolled participants to all individuals approached), and loss to follow-up (proportion of participants who do not complete post-intervention assessments). A benchmark to determine feasibility is \< 40% loss to follow-up.

Acceptability will be measured with qualitative, open-ended to assess participant experience in the intervention and gather information for improving the protocol in future studies. Of particular attention will be the tolerability of a remote, home-based exercise intervention with a semi supervised format.

The Rating of Perceived Exertion (RPE) scale asks respondents to rate the intensity of exercise on a 1-10 scale, with higher values representing greater perceived exertion (1 = Very Light Activity, 10 = Maximum Possible Exertion). The measure has been validated for estimating both aerobic and resistance exercise exertion levels, providing a standard measure across intervention modalities. The average RPE for full-intensity sessions (the first few weeks involve an increasing RPE across sessions) will be calculated for each participant.

Participants will complete an RPE rating after each session. These ratings will be used to calculate adherence rate for each participant. A session with an RPE that is at or above the intended RPE will be considered adherent. The number of adherent sessions will be divided by the total number of sessions, whether the session was attended or not. The participant adherence rates will be averaged to find a mean adherence rate per participant.

This is operationalized as maximal exercise capacity, which is ascertained by measuring peak oxygen consumption (volume oxygen \[VO2\] peak) during cardiopulmonary exercise testing (CPET). All CPETs will be administered by a trained exercise physiologist using the Modified Bruce protocol, an appropriate testing paradigm for people with reduced physical functioning. This procedure will estimate the VO2 (absolute).

This is operationalized as maximal exercise capacity, which is ascertained by measuring peak oxygen consumption (volume oxygen \[VO2\] peak) during cardiopulmonary exercise testing (CPET). All CPETs will be administered by a trained exercise physiologist using the Modified Bruce protocol, an appropriate testing paradigm for people with reduced physical functioning. This procedure will estimate the VO2 (relative to bodyweight).

Submaximal exercise capacity, also considered functional capacity, will be determined with the six minute walk test (6MWT), which measures the distance a person can walk in six minutes (6MWD). A widely used measure of submaximal exercise capacity, the 6MWT will be administered at all study timepoints to evaluate intervention response.

Prior to the measurement of body weight, participants will be instructed to remove heavy clothing and empty pockets of their contents. Weight will be measured to the nearest one-tenth kg with a calibrated balance beam or digital scale.

Hip circumference will be measured to the nearest one-tenth cm.

Height will be measured while the participant stands without shoes using a wall-mounted stadiometer to the nearest one-tenth cm.

Subcutaneous (SQ) fat and visceral adipose tissue (VAT) will be assessed via abdominal MRI. For analysis, fat depots will be separated into abdominal SQ fat and VAT which will be further segmented into intraperitoneal (IP) and retroperitoneal (RP) fat using commercially available software. SQ fat will be defined as the fat outside the muscular abdominal wall; IP fat as fat within the mesentery and omentum bounded anteriorly and laterally by the abdominal wall and posteriorly by a curved line drawn between the kidneys; RP fat as the remaining fat. Adipose tissues will be segmented and colored from other tissues based on pixel intensity and known divisions of tissue planes. The MRI analyst, blinded to participant characteristics, will correct any misidentified fat or non-fat regions using manual tools provided within the software. To calculate each of the compartmental fat deposits, the number of subpixels within each fat compartment.

The ratio of thigh IMF to skeletal muscle (SM) will be ascertained via magnetic resonance imaging (MRI) by trained MRI technologists. Participants will undergo a screening process with the MRI technologist to ensure that eligibility criteria for MRI scans are met. Participants will then change into a hospital gown and enter the MRI scanner. In this longitudinal assessment of IMF, the MRI technologist will be instructed to match participant scan positions across time by matching the current scan position with the participant's previous scan position, recorded at the timepoint prior. MRI analysts will quantitate total and compartment amounts of muscle and adipose tissue using cross-sectional areas of thigh skeletal muscle (SM) and IMF using commercially available software. Thigh IMF area will be calculated as the number of fat pixels within the thigh musculature multiplied by the pixel surface area.

Waist circumference will be measured to the nearest one-tenth cm.

The Short Form Health Survey-36 (SF-36) is a widely used self-report measure of quality of life and health status. Comprised of 36 multiple choice questions, the SF-36 queries general perceptions a participant has about their health, as well as limitations to physical activity, physical health problems, mental health problems, pain, and energy/fatigue. The SF-36 is used across health research domains, and in breast cancer has been validated as a reliable longitudinal monitor of quality of life.

Time spent engaging in physical activity will be measured with the Physical Activity Recall Interview. The PAR assesses time spent in physical activity over the past 7 days.

Participants' perception of their current well-being will be assessed with the 28-item 5-point Likert scale Functional Assessment of Cancer Therapy (FACT)-General. The FACT-G contains 4 subscales measuring physical, social, emotional, and functional well-being and has been validated for reliably measuring well-being in cancer patients.

Time spent engaging in sedentary lifestyle behaviors will be measured with the self-administered Sedentary Behaviors Questionnaire (SBQ). The SBQ measures the minutes spent participating in 9 different sedentary behaviors per "typical" weekday and weekend day.

The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale is a 13-item scale originally developed for and widely used to assess cancer-related fatigue. The FACIT-Fatigue scale measures severity (i.e., "I feel fatigued"; "I feel weak all over") and impact of fatigue (e.g., "I need help doing my usual activities"; "I have to limit my social activity because I am tired") over the past week, with responses scored on a 5-point scale, from 0 "not at all" to 4 "very much." The FACIT-Fatigue scale has excellent psychometric properties and a focus on physical aspects of fatigue.