Exercise Program in Cancer and Cognition

Study Overview
=================
Brief Summary
-----------------
This randomized control trial will examine whether a well-controlled and monitored exercise intervention improves cognitive function in postmenopausal women with early-stage breast cancer and will explore whether neuroimaging metrics of brain health, pro-inflammatory biomarkers and symptoms (fatigue, sleep problems, depression, anxiety) mediate the effects of exercise on cognitive function. Furthermore, the study will explore whether the magnitude of the improvements in cognitive function are modified by estradiol levels.

Detailed Description
-----------------
The specific aims include: Compared to usual care, examine whether the 6-month exercise intervention improves cognitive function in postmenopausal women with early stage breast cancer. Hypothesis 1. Exercise will improve cognitive function in women in a domain specific fashion such that attention, executive and memory functions will be influenced more than other domains. Compared to usual care, examine the direct effects of exercise on neuroimaging metrics of brain health including regional gray matter volume, white matter architecture and functional dynamics of the brain and the pro-inflammatory biomarkers (IL-6 as primary outcomes; TNF-α as secondary), and explore the direct effects of exercise on symptoms (fatigue, sleep problems, depression, anxiety). Hypothesis 2. Exercise will improve neuroimaging metrics of brain health and pro-inflammatory biomarkers. Compared to usual care, explore whether the effects of exercise on cognitive function are mediated by a) neuroimaging metrics of cognitive function, b) IL-6 and TNF-α levels and c) symptoms (fatigue, sleep problems, depression, anxiety), and moderated by E2 levels.

Official Title
-----------------
Influence of Exercise on Neurocognitive Function in Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Behavioral: Moderate-Intensity Aerobic Exercise Intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Postmenopausal female Maximum age 80 years Able to speak and read English Minimum completion of 8 years of education Diagnosed with Stage 0, 1, 2 or 3a Breast Cancer Within 2 years post-completion of primary treatment At least two weeks post-breast conserving surgery or three weeks post-breast conserving surgery with sentinel lymph node biopsy or four weeks post-mastectomy Exclusion Criteria: 1. Prior treatment with cancer chemotherapy, central nervous system radiation, or intrathecal therapy 2. Clinical evidence of distant metastases 3. Self-report of hospitalization for psychiatric illness within the last two years 4. History of neurologic illness 5. Any of the following breast cancer surgery complications unless approved by the participant's health care provider: persistent seroma requiring aspiration, wound dehiscence, infection, prolonged drain output, lymphedema 6. Reconstructive surgery unless approved by the participant's health care provider 7. Any significant medical condition that would preclude them from exercising (e.g., uncontrolled diabetes, congestive heart failure, angina, uncontrolled arrhythmia or other symptoms that indicate increased risk for an acute cardiovascular or respiratory event) If necessary, we will verify this information with a participant's health care provider 8. Eating disorders or a history of substance abuse 10. Any use of an assisted walking device 11. Recent history of falls or balance problems Additional Exclusion Criteria for Neuroimaging subgroup: 1. Presence of metal implants (i.e., pacemaker, some stents)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate-intensity aerobic exercise<br>Participants engage in a supervised 6-month moderate-intensity aerobic exercise intervention. | Behavioral: Moderate-Intensity Aerobic Exercise Intervention<br>* The intervention is moderate-intensity aerobic exercise. Walking on a motorized treadmill will be the encouraged mode of exercise; however participants may use other equipment or home exercise. Participants will begin by exercising 10-15 minutes for 3 days/week during the first 2 weeks and gradually increase the duration for the following 4 weeks until they reach 40-50 minutes per session/3 days per week. This level is then maintained for the remainder of the 6 months. The rate of increase will be tailored based on baseline cardiorespiratory fitness and response to exercise. All sessions start and end with a vital sign check (in-person) and 5-10 minutes warm-up/cool-down. Trained exercise physiologists will supervise all exercise sessions and closely monitor adherence, intensity, and safety when sessions are completed in-person, or through regular communication when home-based exercise is warranted (due to COVID-19).<br>|
| No Intervention: Usual Care<br>Physical activity neither limited nor withheld. Participants engage in activity in the same manner as if they were not part of an active intervention. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function | A comprehensive neuropsychological battery to assess 6 domains of cognitive function (attention, learning and memory, executive function, mental flexibility, psychomotor efficiency, visuospatial ability) | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuroimaging metrics of brain health | fMRI will be used to measure regional gray matter volume, white matter architecture and functional dynamics of the brain. | Baseline and 6 months | 
| Pro-inflammatory cytokines |  | Baseline and 6 months | 
| Cardiovascular Fitness (submaximal VO2) | Fitness will be measured by submaximal VO2 test. The submaximal test is similar to the full test, but stops at 85% of the age-predicted heart rate. The protocol involves walking at a self-selected pace between 2.0-4.0 mph with increasing grade increments of 2% every two minutes. The test is terminated when the subject reaches 85% of their age-predicted heart rate or at volitional exhaustion. | Baseline and 6 months | 
| Energy expenditure (SenseWear physical activity-monitoring armband) | Energy expenditure will be measured using SenseWear physical activity-monitoring armbands. This armband is worn around the upper arm (left triceps) for 1 week at a time. | Baseline, 3.5 months and 7 months | 
| Estradiol (E2) levels |  | Baseline and 6 months | 
| Fatigue | The Fatigue 8a Patient Reported Outcomes Measurement Information System (PROMIS) short form will be used to measure fatigue. | Baseline and 6 months | 
| Anxiety | The Anxiety 8a PROMIS short form will be used to measure anxiety. | Baseline and 6 months | 
| Sleep problems | Sleep problems will be measured using SenseWear physical activity-monitoring armband. | Baseline and 6 months | 
| Sleep problems | Sleep problems will be measured using the Pittsburgh Sleep Quality Index. | Baseline and 6 months | 
| Sleep problems | Sleep problems will be measured using the Epworth Sleepiness Scale. | Baseline and 6 months | 
| Depressive symptoms | Depressive symptoms will be measured using the Beck Depression Inventory II. | Baseline and 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alteration, Cognitive Function, Exercise