Breast Cancer, Reasoning, and Activity Intervention

Study Overview
=================
Brief Summary
-----------------
The objective of the proposed study is to test the effectiveness of aerobic exercise training, delivered in a community-based setting, for improving cognitive function in post-menopausal Breast Cancer Survivors (BCS).

Detailed Description
-----------------
Aim 1: This study will compare changes in cognitive function and brain health in post-menopausal breast cancer survivors (BCS) randomized to either: 1) a community-based aerobic exercise program; or 2) a health education program (control group). Aim 2: Gather information on the intervention's potential for scalability using the RE-AIM framework. Eligible BCS (N=160) will be randomized to one of the following 6-month programs: Aerobic Exercise Training (n=80; progressive moderate-intensity exercise delivered by community fitness center personal trainers) or Health Education (n=80; attention control receiving cancer support and education). To assess Aim 1, participants will complete measures at baseline (Month 0), post-intervention (Month 6), and follow-up (Month 12; i.e., 6 months after post-intervention). Aim 1 measures include: neurocognitive tasks, functional magnetic resonance imaging (fMRI; M0 and M6 only), graded exercise testing, physical activity monitoring (i.e., accelerometry), and questionnaires. To assess Aim 2, outcomes defined by the RE-AIM framework (a dissemination and implementation framework) will be measured, including: study reach(e.g., participation rate), intervention effectiveness (i.e., Aim 1), intervention adoption (e.g.,number of community sites invited that participate), implementation (e.g., fidelity of intervention delivery, participant satisfaction), and maintenance (e.g., Aim 1 maintenance of effects, participant retention). Findings of this study will lay the groundwork toward our long-term goal of disseminating an evidence-based program for managing cognitive impairment in individuals diagnosed with cancer.

Official Title
-----------------
Enhancing Cognitive Function in Breast Cancer Survivors Through Community-based Exercise Training

Conditions
-----------------
Breast Cancer, Breast Neoplasms

Intervention / Treatment
-----------------
* Behavioral: Aerobic Exercise Training
* Other: Health Education (Active comparator)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Able to provide medical record release to confirm eligibility First, primary diagnosis of Stage I-IIIa breast cancer Post-menopausal at the time of diagnosis Post-surgery and completed primary treatment (i.e., surgery, chemotherapy, and/or radiation therapy) 3-24 months prior to enrollment No evidence of possible cognitive impairment as assessed using the Telephone Interview of Cognitive status (TICS-M) Self-report 20+ minutes of exercise on 2 or fewer days per week within the previous six months Receive physician's clearance to participate in an exercise program Ability to complete assessments by themselves or with assistance Exclusion Criteria: Pre- or peri-menopausal at the time of diagnosis with breast cancer Stage 0 breast cancer diagnosis OR metastatic disease Currently receiving or <3 months since receiving chemotherapy or radiation therapy for cancer, or greater than 24 months post primary treatment Planned surgery during the intervention period Second cancer diagnosis (excluding non-invasive skin cancers; including breast cancer recurrence) History of stroke, transient ischemic attack, other neurological disorders, or brain surgery involving tissue removal as confirmed via clinical determination Clinically significant TICS-M score Not able to provide physician re-clearance for exercise if required based upon clinically significant baseline exercise test Contraindications to functional magnetic resonance imaging (fMRI) in accordance with the Mayo Clinic Department of Radiology safety protocols Clinically significant MRI scan as determined by physician review in which the following is advised via radiologist overread: remarkable/abnormal limited diagnostic brain image with recommended medical follow-up Enrolled in another physical activity program Unable to walk without assistance or devices Unwilling to complete study requirements Unwilling to be randomized to the exercise group or health education group Unable or unwilling to continuously wear and regularly sync/charge an activity tracker during the study period Unable to travel regularly to the study locations for intervention sessions and data collection Unwilling to return to enrolling institution for follow-up

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise Training<br>Breast cancer survivors randomized to the intervention group will participate in a moderate-intensity aerobic exercise program for 24 weeks. | Behavioral: Aerobic Exercise Training<br>* Breast cancer survivors in the intervention group will participate in a 24-week moderate intensity exercise program led by community-based fitness center personal trainers. 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. Treadmill walking is the primary mode of exercise. However, participants will be permitted to use other cardiovascular equipment (e.g., elliptical machines, stationary bicycles) as prescribed by their exercise trainer. The trainer will supervise three weekly exercise sessions in Weeks 1-2, two in Weeks 3-4, one in Weeks 5-8, biweekly across weeks 9-16, and monthly in Weeks 17-24 (N=20 supervised sessions).<br>|
| Active Comparator: Health Education (Control)<br>Individuals randomized to Health Education will receive individual education and counseling related to general cancer-related health and support across 24 weeks. | Other: Health Education (Active comparator)<br>* Breast cancer survivors in the Health Education group will participate in education sessions with a health educator and receive monthly newsletters/webinars (N=20 total contacts) across 24 weeks. The program will include cancer support and discussion of cancer-related wellness topics (e.g., stress management, coping). Control group participants will be offered a 6-month fitness center membership upon study completion.<br>* Other names: Control Group;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in inhibitory control | Change in interference score on Stroop task, with negative values indicating lower inhibitory control. | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in cognitive flexibility | Change in reaction time on Task-switch task, with higher values indicating lower cognitive flexibility | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in executive function processing | Change in completion time on Trails B task, with higher values indicating lower executive function. | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| 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 (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in short-term memory | Change in accuracy on N-Back task, with higher accuracy indicating better short-term memory | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in verbal memory | Change in number recalled on Auditory Verbal Learning task, with greater number of items recalled indicating better verbal memory | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in relational memory | change in response time, with shorter response time associated with faster relational memory processes | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in spatial working memory accuracy | Change in accuracy on Flanker task, with greater accuracy indicating better working memory | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 
| Change in brain volume | change in mean cortical thickness of brain regions of interest as measured by an anatomic MRI brain scan | baseline (Month 0), post-intervention (month 6) | 
| Change in white matter integrity | change in fractional anisotropy as measured by diffusion MRI. | baseline (Month 0), post-intervention (month 6) | 
| Change in resting state functional connectivity | change in within-network pairwise correlation estimates as measured using a multiband echo planar imaging (mb-EPI) functional MRI sequence | baseline (Month 0), post-intervention (month 6) | 
| Change in self-reported cognitive function | The perceived cognitive impairments subscale of the Functional Assessment in Cancer Therapy - Cognition (FACT-Cog) will be used to measure self-reported cognition. Scores range from 0-72, with higher scores indicating better cognitive function. | baseline (Month 0), post-intervention (month 6), follow up (month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reach | Participation rate among eligible individuals contacted about the study. | baseline (Month 0) | 
| Adoption | sociodemographics questionnaire to describe demographics characteristics and experience among personal trainers | post-intervention (month 6) | 
| Implementation | percent of session checklist items completed as intended | post-intervention (month 6) | 
| Maintenance | The number of participants who withdraw during the follow-up period. | follow up (month 12) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
physical activity, exercise, cognition, brain health, breast cancer