High-intensity Exercise After Treatment

Study Overview
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Brief Summary
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This pilot study tests the feasibility and preliminary efficacy of an 8-week, 3-arm pilot exercise trial in which 45 breast cancer survivors will be randomized to high-intensity interval training (HIIT; n=15), moderate-intensity aerobic training (MOD; n=15), or Usual Care (UC; n=15).

Detailed Description
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Aim 1: Determine the feasibility and acceptability of an 8-week high-intensity interval training (HIIT) program compared with a standard moderate-intensity aerobic training (MOD) program in 45 breast cancer survivors prescribed aromatase inhibitors. Aim 2: Calculate effect sizes associated with the 8-week HIIT program, compared with MOD and Usual Care (UC), on cognitive and cardiovascular functions in 45 breast cancer survivors. Eligible individuals will be women diagnosed with Stages I-IIIa breast cancer, have completed primary treatment (i.e., surgery, chemotherapy, and/or radiation therapy), and currently prescribed an aromatase inhibitor. The specific aims are: 1) Determine the feasibility and acceptability of an 8-week high-intensity interval training (HIIT) program compared with a standard moderate-intensity (MOD) program; and 2) Calculate effect sizes associated with the 8-week HIIT program, compared with MOD and usual care (UC), on cognitive and cardiovascular functions. Cognitive function is operationalized as performance on executive function and working memory tasks. Cardiovascular function is operationalized as exercise capacity (VO2peak, heart rate recovery), resting function (heart rate, blood pressure), and cardiovascular structure/function (arterial stiffness, arterial wall thickness, endothelial function). Associations between change in cardiovascular outcomes and change in cognitive outcomes across the intervention period will also be explored.

Official Title
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Enhancing Cognitive and Cardiovascular Function in Breast Cancer Survivors Through High-intensity Interval Training

Conditions
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Breast Cancer, Breast Neoplasm Female

Intervention / Treatment
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* Behavioral: High-Intensity Interval Training
* Behavioral: Moderate-Intensity Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult female (aged 19 or older) First, primary diagnosis of Stage I-IIIa breast cancer Hormone receptor positive (ER+ and/or PR+) diagnosis Human epidermal growth factor receptor 2 negative (HER2-) diagnosis Completed primary adjuvant treatment (i.e., surgery, chemotherapy, and/or radiation therapy) Currently prescribed an aromatase inhibitor No evidence of possible cognitive impairment as assessed using the Telephone Interview of Cognitive Status (TICS-M; score >21) Sedentary except for casual lifestyle recreation. This is defined as self-reporting 20+ minutes of exercise physical activity on 2 or fewer days per week within the previous six months. Receive physician's clearance to participate in an exercise program Agree to be randomized Fully vaccinated for COVID-19 ≥2 weeks prior to participation Provide written informed consent to participate in study Exclusion Criteria: Males. Stage 0 breast cancer diagnosis or metastatic disease Currently receiving chemotherapy or radiation therapy for any cancer Scheduled to receive breast surgery (e.g., mastectomy, reconstructive surgery) during the study period Second cancer diagnosis (excluding non-invasive skin cancers; including breast cancer recurrence) Self-report an 20+ minutes of exercise physical activity on 3+ days per week for the previous 6 months Pregnant or plan to become pregnant during study period. Is not cleared to participate in exercise by a physician. Enrolled in another physical activity program Unable to cycle on a stationary bike Unwilling to complete study requirements History of stroke, transient ischemic attack, other neurological disorders, or brain surgery involving tissue removal Clinically significant TICS-M score (<21) during baseline procedures Not fully vaccinated for COVID-19

Ages Eligible for Study
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Minimum Age: 19 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Intensity Interval Training (HIIT)<br>Breast cancer survivors randomized to HIIT will participate in a high-intensity interval training program for 8 weeks. | Behavioral: High-Intensity Interval Training<br>* HIIT is a type of training in which short periods of high-intensity anaerobic exercise (1-4 minutes at 80-95% of VO2peak) are alternated with less intense aerobic recovery periods (1-3 minutes at 50-60% VO2peak). Individually-tailored exercise prescriptions will be developed based upon each participant's baseline maximal graded exercise test (heart rate corresponding with %VO2 peak) and symptom limitation. Sessions will be progressive in nature such that the volume of exercise (i.e., number and intensity of intervals) increases across weeks. Intervals will progress from a heart rate corresponding with 75% VO2peak in Week 1 to 90-95% VO2peak in Weeks 5-8. Sessions will be  30 minutes in length. Indoor cycling is the primary mode of exercise.<br>|
| Active Comparator: Moderate-Intensity Exercise (MOD)<br>Breast cancer survivors randomized to MOD will participate in a moderate-intensity aerobic exercise program for 8 weeks. | Behavioral: Moderate-Intensity Exercise<br>* Individually-tailored exercise prescriptions will be developed based upon each participant's baseline maximal graded exercise test (heart rate corresponding with %VO2 peak) and symptom limitation. Sessions will be progressive in nature such that the volume of exercise increases across weeks. Indoor cycling is the primary mode of exercise. Sessions will include moderate-intensity cycling that progresses from a heart rate corresponding with 55-60% VO2peak for 30 minutes in Week 1 to 65-70% VO2peak for 45-50 minutes in Weeks 5-8.<br>|
| No Intervention: Usual Care (UC)<br>Individuals randomized to UC will be instructed to continue standard cancer care and engage in habitual lifestyle behaviors. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participation Rate | Sample size / [1-(#ineligible/# exposed to recruitment)*(#exposed to recruitment)] | Baseline | 
| Adherence to the exercise programs | average number of exercise sessions (out of 24) attended | post-intervention (Week 9) | 
| Compliance of the exercise programs | average number of exercise sessions (out of 24) in which the prescribed exercise duration and intensity are achieved | post-intervention | 
| Acceptability of the exercise programs | satisfaction with the exercise program as measured by a satisfaction survey. Survey uses a 5-point Likert-type scale. Satisfaction for each item is defined as reporting 4-5 on the scale (i.e., somewhat agree or completely agree). | post-intervention | 
| Change in executive function processing | Change in completion time on Trails B task, with higher values indicating lower executive function. | Baseline, post-intervention (Week 9) | 
| Change in cognitive flexibility | Change in reaction time on Task-switch task, with higher values indicating lower cognitive flexibility | Baseline, post-intervention (Week 9) | 
| Change in spatial working memory reaction time | Change in reaction time on spatial working memory task, with faster reaction times indicating better spatial working memory | Baseline, post-intervention (Week 9) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiorespiratory Fitness | Change in Peak VO2 as measured by a modified Balke treadmill graded exercise test protocol. | Baseline, post-intervention (Week 9) | 
| Carotid arterial wall thickness | will be estimated from vascular ultrasound and expressed as average and maximum mm | Baseline, post-intervention (Week 9) | 
| Endothelial function | estimated from brachial artery flow mediated dilation and expressed as percent change in brachial artery diameter relative to baseline diameter | Baseline, post-intervention (Week 9) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise, breast cancer, physical activity, cognitive function, cardiovascular function