Clinical trial NCT02793921: Exercise Program in Cancer and Cognition
Official title: Influence of Exercise on Neurocognitive Function in Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: Alteration
Cognitive Function
Exercise
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2016-06-08
Enrollment: 153
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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:

1. 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.
2. 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.
3. 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.

Eligibility criteria: Inclusion Criteria:

1. Postmenopausal female
2. Maximum age 80 years
3. Able to speak and read English
4. Minimum completion of 8 years of education
5. Diagnosed with Stage 0, 1, 2 or 3a Breast Cancer
6. Within 2 years post-completion of primary treatment
7. 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)

Primary outcomes:
measure: Change in Cognitive Function
timeFrame: Baseline to 6 months
Secondary outcomes:
measure: Total Brain Size
timeFrame: Baseline and 6 months
measure: Pro-inflammatory Cytokines
timeFrame: Baseline to 6 months
measure: Peak VO2
timeFrame: Baseline and 6 months
measure: Estradiol (E2) Levels
timeFrame: Baseline to 6 months
measure: Fatigue
timeFrame: Baseline and 6 months
measure: Anxiety
timeFrame: Baseline to 6 months
measure: Sleep Problems
timeFrame: Baseline to 6 months
measure: Depressive Symptoms
timeFrame: Baseline to 6 months
Other outcomes:
measure: Change in White Matter Microstructure
timeFrame: Baseline and 6 months
measure: Changes in Prefrontal Cortex
timeFrame: Baseline and 6 months
measure: Changes in Task-evoked Functional MRI Outcomes
timeFrame: Baseline and 6 months
measure: Changes in Resting State Network
timeFrame: Baseline and 6 months
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Catherine M Bender, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Kirk I Erickson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bender CM, Sereika SM, Gentry AL, Duquette JE, Casillo FE, Marsland A, Brufsky AM, Evans S, Gorantla VC, Grahovac TL, McAuliffe PF, Steiman JG, Zhu Y, Erickson KI. Physical activity, cardiorespiratory fitness, and cognitive function in postmenopausal women with breast cancer. Support Care Cancer. 2021 Jul;29(7):3743-3752. doi: 10.1007/s00520-020-05865-4. Epub 2020 Nov 19.
citation: Gentry AL, Erickson KI, Sereika SM, Casillo FE, Crisafio ME, Donahue PT, Grove GA, Marsland AL, Watt JC, Bender CM. Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy. Contemp Clin Trials. 2018 Apr;67:109-115. doi: 10.1016/j.cct.2018.02.012. Epub 2018 Mar 6.