Exercise Program in Cancer and Cognition

Breast Cancer Clinical Trial

— EPICC  

Official title:

Influence of Exercise on Neurocognitive Function in Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02793921
• Other study ID #: STUDY19080223
• Secondary ID: 1R01CA196762-01A
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: January 10, 2023

Study information

• Verified date: January 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: January 10, 2023
• Est. primary completion date: January 10, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Behavioral:
• Moderate-Intensity Aerobic Exercise Intervention
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).

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pittsburgh	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in White Matter Microstructure		Baseline and 6 months
Other	Changes in Prefrontal Cortex		Baseline and 6 months
Other	Changes in Task-evoked Functional MRI Outcomes		Baseline and 6 months
Other	Changes in Resting State Network		Baseline and 6 months
Primary	Change in Cognitive Function	Cognitive function was assessed with a battery of 14 measures. A data reduction technique, exploratory factor analysis with principal component extraction and varimax (orthogonal) rotation, was used to create summary factors. The cognitive factors identified included processing speed, attention, mental flexibility, working memory, learning and memory, verbal memory, and executive function were derived via this factor analysis. Individual measures with the highest loadings were included in each factor. All measures had factor loadings >0.400. Scores from the individual measures for each factor were normed based on healthy controls of similar age and education to yield a z-score and these were summed to yield an average z-score for each factor. Z-scores range from -4 to +4, where higher z-scores indicate better performance for each factor.	Baseline to 6 months
Secondary	Total Brain Size	High-resolution anatomical MPRAGE (1mm3 voxels, 256 slices) images will be used for volumetric analyses. The FreeSurfer pipeline using its longitudinal option will be employed to compute cortical volumes.	Baseline and 6 months
Secondary	Pro-inflammatory Cytokines	Cytokine levels for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were determined using high-sensitivity, quantitative sandwich enzyme immunoassay run according to manufacturer's directions. Greater pgs/ML indicate higher levels of both IL-6 and TNF-aplha.	Baseline to 6 months
Secondary	Peak 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. Higher levels (ml/kg/minute) indicate better peak VO2.	Baseline and 6 months
Secondary	Estradiol (E2) Levels	E2 was determined by a competitive binding immunoassay, according to manufacturer's directions. Greater pgs/ML indicate higher levels of estradiol.	Baseline to 6 months
Secondary	Fatigue	The Fatigue 8a Patient Reported Outcomes Measurement Information System (PROMIS) short form was used to measure fatigue. It consists of 8 items on which participants respond using a 5-point Likert scale. The scores range from 0 to 24 with higher scores indicating greater fatigue.	Baseline and 6 months
Secondary	Anxiety	The eight-item Anxiety 8a PROMIS short form was used to measure anxiety. Participants rate each item on a scale from 1 to 5. The score is the total of the responses with higher scores indicating greater anxiety. The range of scores is 5 to 40.	Baseline to 6 months
Secondary	Sleep Problems	Sleep problems were measured using global score of the Pittsburgh Sleep Quality Index (PSQI). The PSQI is a self-report measure that consists of 19 items. Each item is weighted on a 0-3 interval scale. The PSQI global score ranges from 0 to 21, where lower scores indicate better sleep quality, and higher scores indicate poorer sleep quality.	Baseline to 6 months
Secondary	Depressive Symptoms	Depressive symptoms will be measured using the Beck Depression Inventory II (BDI II). The 21-item BDI II is a self-report measure on which participants rate depressive symptoms on a four-point scale. The BDI II score ranges from 0 to 63 with higher scores indicating greater depressive symptomatology.	Baseline to 6 months