Breast Cancer, Reasoning, and Activity Intervention (BRAIN)

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Breast Neoplasms; Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Cancer-related Cognitive Dysfunction
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Behavioral: Aerobic Exercise Training; Other: Medical Device Usage and Evaluation; Other: Health Education (Active comparator)

Detailed Description

PRIMARY OBJECTIVES:

I. Examine the effectiveness of a 6-month, community-based aerobic exercise intervention on multiple indicators of cognitive function in post-menopausal breast cancer survivors.

II. Gather information on the intervention's potential for scalability using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework.

EXPLORATORY OBJECTIVE:

I. Explore potential moderators and mediators of the effects of aerobic exercise training on cognitive function.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients attend 3 weekly exercise sessions in weeks 1-2, 2 sessions each week in weeks 3-4, 1 session each week in weeks 5-8, biweekly sessions across weeks 9-16, and monthly sessions in weeks 17-24 for a total of 20 supervised sessions. Patients undergo magnetic resonance imaging (MRI) and wear an accelerometer throughout the study.

ARM II: Patients receive 6 in-person and 9 digital educational sessions and 5 monthly educational newsletters for a total of 20 contacts across 24 weeks. Patients undergo MRI and wear an accelerometer throughout the study.

After completion of study intervention, patients are followed up with at 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
• Study Contact Backup: Name: Gabriella Hickman, MS; Phone Number: 480-574-1369; Email: Hickman.Gabriella@mayo.edu

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
      • Principal Investigator: Diane K. Ehlers, Ph.D.
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu
      • Contact: Gabriella Hickman, MS; Phone Number: 480-574-1369; Email: Hickman.Gabriella@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

BREAST CANCER SURVIVOR PARTICIPANTS:

• Adult female (aged 19 or older)
• Post-menopausal at time of breast cancer diagnosis defined as no menses for at least 12 months prior to diagnosis. We are targeting post-menopausal women only because: (1) 93% of breast cancer diagnoses are in women 50 years of age and older; and (2) evidence suggests cancer treatment-induced amenorrhea may be independently associated with cancer-related cognitive impairment (CRCI), which, could interfere with our ability to successfully test our specific aims. In an effort to reduce any confounding effects this factor may have on our analyses, we have, under the guidance of co-investigator Reed, decided to exclude women who were pre- or peri menopausal at diagnosis. Finally, due to the interaction between aging and cancer, post-menopausal survivors may be at greatest risk of cognitive decline after breast cancer diagnosis
• First, primary diagnosis of stage I-IIIa breast cancer

• Post-surgery and completed primary adjuvant treatment (i.e., surgery, chemotherapy, and/or radiation therapy) 3-24 months prior to study start. No exclusion criteria relative to type(s) of adjuvant therapy received will be applied in this study. Women currently prescribed adjuvant endocrine therapy (e.g., aromatase inhibitor, estrogen receptor down-regulator, selective estrogen receptor modulator) will be eligible to participate.

  • Although, CRCI has been reported in cancer survivors up to 20 years after the end of treatment, we have chosen to focus our study on women 3-24 months post-treatment. Our previous work demonstrated significant effects of physical activity on cognitive function in women ~8 years from their breast cancer diagnosis. However, recent clinical exercise trials have observed significant effects on cognitive functions in women up to two years after their diagnosis. Additionally, previous studies suggest the first year post-treatment may represent a teachable moment relative to lifestyle behavior adoption and cancer rehabilitation. As such, we will focus recruitment on the first two years post-treatment and will actively monitor recruitment as part of Specific Aim 2.
• We have chosen not to exclude women who did not receive chemotherapy for their cancer because deficits in cognition have been observed in women before receipt of adjuvant chemotherapy and in women who did not receive chemotherapy for their breast cancer. We agree that receipt of chemotherapy may exacerbate the cumulative effects of a cancer diagnosis on cognitive function; however, the currently available scientific evidence in this area does not warrant excluding women who have not received chemotherapy for their breast cancer.
• No evidence of possible cognitive impairment as assessed using the Mini-Mental State Exam (MMSE; score > 23)
• 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
• Successful completion of graded exercise test without evidence of cardiac abnormalities or responses
• Agree to be randomized to an exercise group or health education group

• Wearable sensor specific criteria:

  • Compatible mobile device, laptop computer, or desktop computer
  • Willingness to continuously wear the Actigraph GT9X Link device during waking hours for the duration of the study period
  • Willingness and ability to charge the Actigraph device at home once per week.
  • Willingness and ability to sync the Actigraph device at home once per day

PERSONAL TRAINER PARTICIPANTS:

• 19 years-old or older
• Nationally accredited personal trainer, exercise physiologist, or other related certification
• Employed at least part-time at the Young Men's Christian Association (YMCA) of Greater Omaha
• Willing to complete all study procedures as outlined in the consent form and fitness center letters of support, including participate in a training in preparation for the exercise intervention, willing to complete activities required to implement the exercise intervention, and willing to complete an interview with the research team after completing the study

Exclusion Criteria:

BREAST CANCER SURVIVOR PARTICIPANTS:

• Female who was pre- or peri-menopausal at the time she was diagnosed with breast cancer
• Stage 0 breast cancer diagnosis or metastatic disease
• Currently receiving chemotherapy or radiation therapy for any cancer or greater than 24 months post-treatment
• 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+ minute of exercise physical activity on 3+ days per week for the previous 6 months

• Is not cleared to participate in exercise by a physician. Individuals with the following conditions/diagnoses will be required to provide clearance for exercise from their cardiologist:

  • History of major multiple myocardial infarctions (MI)
  • Recent electrocardiogram (ECG) changes or recent MI
  • Resting or unstable angina
  • Significant multivessel coronary occlusion (> 70%) on angiography
  • Uncontrolled and/or serious arrhythmias
  • 3rd degree heart block
  • Acute congestive heart failure or ejection fraction < 30%
• 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
• Unwilling to continuously wear and regularly synchronize(sync)/charge the Actigraph device during the study period
• Unwilling to provide written informed consent to participate
• History of stroke, transient ischemic attack, other neurological disorders, or brain surgery involving tissue removal
• Clinically significant MMSE score (< 24) during baseline procedures
• Evidence of abnormal cardiac responses or conditions during graded exercise testing
• Contraindications to functional magnetic resonance imaging (fMRI) in accordance with University of Nebraska Medical Center (UNMC) Core for Advanced MRI (CAMRI) safety protocols

PERSONAL TRAINER PARTICIPANTS:

• Not willing to adhere to study requirements
• Participants will be withdrawn if their employment at the fitness center ends

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Exercise Training; Breast cancer survivors randomized to the intervention group will participate in a moderate-intensity aerobic exercise program for 24 weeks.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; Magnetic resonance imaging (procedure); Behavioral: Aerobic Exercise Training; 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).; Other: Medical Device Usage and Evaluation; Wear accelerometer; Other Names: Accelerometer
Active Comparator: Health Education (Control); Individuals randomized to Health Education will receive individual education and counseling related to general cancer-related health and support across 24 weeks.	Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; Magnetic resonance imaging (procedure); Other: Medical Device Usage and Evaluation; Wear accelerometer; Other Names: Accelerometer; Other: Health Education (Active comparator); 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.; 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)

Other 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 (Month 0), post-intervention (month 6), follow up (month 12)
Change in Cancer-related Fatigue	The Functional Assessment in Chronic Illness Therapy (FACIT) - Fatigue Scale will be used to measure cancer-related fatigue. Scores range from 0-52, with higher scores indicating less cancer-related fatigue.	baseline (Month 0), post-intervention (month 6), follow up (month 12)

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Diane K. Ehlers, Ph.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: physical activity; breast cancer; exercise; cognition; brain health
• Additional Relevant MeSH Terms: Mental Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Neurocognitive Disorders; Breast Diseases; Cognition Disorders; Breast Neoplasms; Cognitive Dysfunction
• Other Study ID Numbers: MC231001; 23-000020 (Other Identifier: Mayo Clinic Institutional Review Board); 852-20-FB (Other Identifier: Previous IRB); R37CA252060 (U.S. NIH Grant/Contract); NCI-2021-09939 (Registry Identifier: Clinical Trials Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Although the final dataset will not include identifying information, there is still a possibility of deductive disclosure of identity. Therefore, data will not be shared via an NIH or approved public repository; however, we will share de-identified data as required for publication in scientific journals and with outside collaborators and scientists upon request.
• IPD Sharing Time Frame: Data will be shared via scientific journals at the time of publication and with outside collaborators before publication.
• IPD Sharing Access Criteria: We will make data available to researchers who agree to use the data only for research purposes, protect the data using secure computer technologies, and destroy the data after relevant analyses are completed and manuscripts published.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No