Breast Cancer, Reasoning, and Activity Intervention

Breast Cancer Clinical Trial

— BRAIN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04816006
• Other study ID #: MC231001
• Secondary ID: 23-000020852-20-
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2024
• Est. completion date: July 31, 2027

Study information

• Verified date: May 2024
• Source: Mayo Clinic
• Contact: Gabriella Hickman, MS
• Phone: 480-574-1369
• Email: Hickman.Gabriella[@]mayo.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial tests whether an exercise intervention works to improve cognitive function in breast cancer survivors. Many breast cancer survivors report cancer-related cognitive impairment, which this has recently become a priority in clinical research due to its dramatic impact on daily functioning, quality of life, and long-term health. Aerobic exercise has the potential to improve cognitive function and brain health in older adults and is recommended as a safe, tolerable, and accessible complementary therapy for breast cancer survivors. This study aims to understand the effects of physical activity compared with health education on memory, attention, and brain health in women with breast cancer. Study findings may help researchers design more programs that can improve memory, attention, and brain health in other women with breast cancer.

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.

II. Investigate the feasibility of urinary metabolites as biomarkers of overall diet patterns.

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 a gait assessment and magnetic resonance imaging (MRI), as well as wear an accelerometer throughout the study.

ARM II: Patients participate in up to 9 monthly classes/webinars. Patients also receive informational portable document format (pdfs), videos, and/or podcasts, and a one-year subscription to the Mayo Clinic Health Letter. Patients undergo a gait assessment and MRI, as well as wear an accelerometer throughout the study.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: July 31, 2027
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• PRE-REGISTRATION: Age =18 years according to participant report and/or clinical determination

• PRE-REGISTRATION: First, primary diagnosis of stage I-IIIa breast cancer according to participant report and/or clinical determination

• PRE-REGISTRATION: Post-menopausal at the time of diagnosis according to participant report and/or clinical determination

• PR1E-REGISTRATION: Post-surgery and completed primary treatment (i.e., surgery, chemotherapy, and/or radiation therapy) 3-24 months prior to registration according to participant report and/or clinical determination

• PRE-REGISTRATION: Sedentary except for casual lifestyle recreation. This is defined as self-reporting 20+ minutes of exercise on 2 or fewer days per week within the previous six months

• PRE-REGISTRATION: Self-reported ability to complete assessments by themselves or with assistance

• REGISTRATION: Age =18 years as confirmed via clinical determination

• REGISTRATION: Able to provide medical record release to confirm eligibility

• REGISTRATION: First, primary diagnosis of stage I-IIIa breast cancer as confirmed via clinical determination

• REGISTRATION: Post-menopausal at the time of diagnosis as confirmed via clinical determination

• REGISTRATION: Post-surgery and completed primary treatment (i.e., surgery, chemotherapy, and/or radiation therapy) 3-24 months prior to registration as confirmed via clinical determination

• REGISTRATION: No evidence of possible cognitive impairment as assessed using the Telephone Interview of Cognitive status (13-item modified version) (TICS-M; score > 21) NOTE: Only individuals who pass the TICS-M during pre-registration will be invited to participate in the urine substudy

• REGISTRATION: Receive physician's clearance to participate in an exercise program

NOTE: Individuals with conditions/diagnoses deemed important by the primary investigator will be required to provide clearance for exercise from their cardiologist. Example conditions include:

• 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%

• REGISTRATION: Ability to complete assessments by themselves or with assistance

Exclusion Criteria:

• PRE-REGISTRATION: Individual who was pre- or peri-menopausal at the time of diagnosis with breast cancer

• PRE-REGISTRATION: Stage 0 breast cancer diagnosis OR metastatic disease

• PRE-REGISTRATION: Currently receiving or < 3 months since receiving chemotherapy or radiation therapy for cancer, or greater than 24 months post primary treatment

• PRE-REGISTRATION: Planned surgery during the intervention period

• PRE-REGISTRATION: Second cancer diagnosis (excluding non-invasive skin cancers; including breast cancer recurrence)

• PRE-REGISTRATION: Unable to travel regularly to the study locations for intervention sessions and data collection

• PRE-REGISTRATION: Unwilling to return to enrolling institution for follow-up

• PRE-REGISTRATION: Self-reported inability to walk without assistance or devices

• REGISTRATION: History of stroke, transient ischemic attack, other neurological disorders, or brain surgery involving tissue removal as confirmed via clinical determination

• REGISTRATION: Clinically significant TICS-M score (< 21) during baseline procedures

• REGISTRATION: Not able to provide physician re-clearance for exercise if required based upon clinically significant baseline exercise test (as determined by ECG and blood pressure monitoring)

• REGISTRATION: Contraindications to functional magnetic resonance imaging (fMRI) in accordance with the Mayo Clinic Department of Radiology safety protocols

• REGISTRATION: 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

• REGISTRATION: Enrolled in another physical activity program

• REGISTRATION: Unable to walk without assistance or devices

• REGISTRATION: Unwilling to complete study requirements

• REGISTRATION: Unwilling to be randomized to the exercise group or health education group

• REGISTRATION: Unable or unwilling to continuously wear and regularly sync/charge an activity tracker during the study period

• REGISTRATION: Unable to travel regularly to the study locations for intervention sessions and data collection

• REGISTRATION: Unwilling to return to enrolling institution for follow-up

Related Conditions & MeSH terms

• Anatomic Stage I Breast Cancer AJCC v8
• Anatomic Stage II Breast Cancer AJCC v8
• Anatomic Stage IIIA Breast Cancer AJCC v8
• Breast Cancer
• Breast Neoplasms
• Cognitive Dysfunction

Intervention

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:
• 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.

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Other:
• Medical Device Usage and Evaluation
Wear accelerometer
• Gait Assessment
Undergo gait assessment test

Locations

Country	Name	City	State
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	Change in white matter integrity	change in fractional anisotropy as measured by diffusion MRI.	baseline (Month 0), post-intervention (month 6)
Primary	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)
Primary	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)
Primary	Reach	Participation rate among eligible individuals contacted about the study.	baseline (Month 0)
Primary	Adoption	sociodemographics questionnaire to describe demographics characteristics and experience among personal trainers	post-intervention (month 6)
Primary	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)
Primary	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)
Primary	Implementation	percent of session checklist items completed as intended	post-intervention (month 6)
Primary	Maintenance	The number of participants who withdraw during the follow-up period.	follow up (month 12)