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

Study Overview
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Brief Summary
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This clinical trial studies the feasibility of implementing various adaptive training exercise programs to improve cardiorespiratory fitness in patients after receiving breast cancer treatment. Information from this study may help researchers better understand how to implement adaptive training interventions to improve cardiorespiratory fitness in patients after receiving breast cancer treatment.

Detailed Description
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OUTLINE: Patients are randomized to the interventional groups or control group. INTERVENTION GROUPS: Patients are randomized to 1 of 2 interventional arms. ARM I: Patients participate in aerobic exercise (AE) sessions 3 times per week for 12 weeks. After 12-weeks, non-responders participate in combined AE and resistance exercise (RE) sessions for an additional 12 weeks, while responders continue participating in the AE sessions alone for an additional 12 weeks. ARM II: Patients participate in RE sessions 3 times per week for 12 weeks. After 12-weeks, non-responders may participate in a further 12-weeks of combined AE and RE sessions, while responders continue participating in the RE sessions alone for an additional 12 weeks. CONTROL GROUP: After 24 weeks, patients receive a digital copy of the 12-week AE sessions and 12-week RE sessions and an outline of sessions for 24 weeks.

Official Title
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Investigating Various Adaptive-Training Exercise Programs for Improving Cardiorespiratory Fitness After Breast Cancer Treatment (ACTIVATE)

Conditions
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Breast Cancer, Invasive Breast Carcinoma

Intervention / Treatment
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* Other: Aerobic Exercise Intervention
* Other: Resistance Exercise Intervention
* Other: Exercise Intervention: Digital copies and outline of sessions
* Other: Questionnaire Administration
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Female gender Prior diagnosis of invasive breast cancer Receipt of chemotherapy or trastuzumab (Herceptin) therapy within the past 6 - 18 months Reduced cardiorespiratory functional capacity, defined as < 80% of age/sex-matched six-minute walk distance (6MWD) (i.e. a 20% shorter distance) Exclusion Criteria: Currently exercising >150 min/week Actively receiving chemotherapy or radiation Medical history of heart failure, coronary artery disease or arrhythmia Contraindications to cardiopulmonary exercise testing (CPET) Contraindications to magnetic resonance imaging (MRI) (e.g ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal; pacemakers, defibrillators, functioning neurostimulator devices, non-compatible MRI tissue expanders or breast implants, or other implanted non-compatible MRI devices), weight over 550 lbs, or symptomatic claustrophobia Contraindications to exercise, including a history of surgery with sequelae that restrict ability to exercise safely or comfortably Unwilling to complete intervention procedures or outcome measures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (aerobic exercise)<br>Patients participate in AE sessions 3 times per week for 12 weeks. After 12-weeks, non-responders participate in combined AE and RE sessions for an additional 12 weeks, while responders continue participating in the AE sessions alone for an additional 12 weeks. | Other: Aerobic Exercise Intervention<br>* Participate in aerobic exercise intervention<br>Other: Resistance Exercise Intervention<br>* Participate in resistance exercise intervention<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Experimental: Arm II (resistance exercise)<br>Patients participate in RE sessions 3 times per week for 12 weeks. After 12-weeks, non-responders may participate in a further 12-weeks of combined AE and RE sessions, while responders continue participating in the RE sessions alone for an additional 12 weeks. | Other: Aerobic Exercise Intervention<br>* Participate in aerobic exercise intervention<br>Other: Resistance Exercise Intervention<br>* Participate in resistance exercise intervention<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| Experimental: Control Group (digital exercise interventions)<br>After 24 weeks, patients receive a digital copy of the 12-week AE sessions and 12-week RE sessions and an outline of sessions for 24 weeks. | Other: Exercise Intervention: Digital copies and outline of sessions<br>* Receive digital copy of AE and RE sessions and an outline of sessions<br>Other: Questionnaire Administration<br>* Ancillary studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intervention feasibility | 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. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intervention safety: adverse events | 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. | Up to 24 weeks | 
| Study feasibility | Study feasibility will be measured by calculating recruitment rates (proportion of enrolled participants to all individuals approached), lost to follow-up (proportion of participants who do not complete post-intervention assessments), relative dose intensity (proportion of completed to planned sessions), early session terminations (proportion of sessions ended by participant prior to completing planned duration), intervention interruptions (missing 3 or more planned sessions consecutively), attendance (proportion of attended to planned sessions), and adherence (gathered from heart rate /accelerometry data and self-report of exercise via questionnaires). A benchmark to determine feasibility is < 40% loss to follow-up. | Up to 24 weeks | 
| Intervention acceptability | 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. | Up to 24 weeks | 
| Intervention session intensity | The Rating of Perceived Exertion (RPE) scale asks respondents to rate the intensity of exercise on a 6 - 20 scale. The measure has been validated for estimating both aerobic and resistance exercise exertion levels, providing a standard measure across intervention modalities. | Up to 24 weeks | 
| Intervention adherence | Participants will wear 2 devices during the study: a waist-worn actigraph and a wrist-worn FitBit activity monitor. The actigraph will be worn for 7 day intervals immediately prior to the baseline and endpoint assessments. In addition, participants will be asked to wear the actigraph 24-hours per day during that 7-day interval with the exception of when engaged in water activities for the duration of their intervention participation. Together, these data will be used to gauge adherence to the exercise intervention. The raw data generated from these devices will be reviewed by a trained accelerometer analyst for quality control and cleaning. Then the analyst will calculate the amount of time (in min/per day) spent in activities of low-, moderate-, and vigorous-activity. Categorization of the level of physical activity will use accepted cut points from the literature. | Up to 24 weeks | 
| Maximal exercise capacity (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 (absolute). | Up to 24 weeks | 
| Maximal exercise capacity (relative to bodyweight) | 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). | Up to 24 weeks | 
| Submaximal exercise capacity | 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. | Up to 24 weeks | 
| Anthropometrics (Weight) | 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. | Up to 24 weeks | 
| Anthropometrics (Height) | Height will be measured while the participant stands without shoes using a wall-mounted stadiometer to the nearest one-tenth cm. | Up to 24 weeks | 
| Anthropometrics (Hip circumference) | Hip circumference will be measured to the nearest one-tenth cm. | Up to 24 weeks | 
| Anthropometrics (Waist circumference) | Waist circumference will be measured to the nearest one-tenth cm. | Up to 24 weeks | 
| Intermuscular fat (IMF) | 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. | Up to 24 weeks | 
| Abdominal deposits of fat | 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. | Up to 24 weeks | 
| Change in quality of life | 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. | Up to 24 weeks | 
| Physical activity and sedentary behaviors (IPAQ) | Time spent engaging in physical activity and in sedentary lifestyle behaviors will be measured with the self-administered International Physical Activity Questionnaire (IPAQ). The IPAQ assesses minutes spent performing moderate or vigorous exercise during activities of daily living over the past week, including exercise. | Up to 24 weeks | 
| Physical activity and sedentary behaviors (SBQ) | Time spent engaging in physical activity and 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. | Up to 24 weeks | 
| Perceived well-being | 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. | Up to 24 weeks | 
| Level of fatigue | 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. | Up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, exercise, fatigue, fitness, aerobic, survivor