Exercise Program in Cancer and Cognition (EPICC)

• ClinicalTrials.gov Identifier: NCT02793921
• Recruitment Status: Completed
• First Posted: June 8, 2016
• Last Update Posted: January 11, 2023
• Sponsor: University of Pittsburgh
• Collaborators: National Institutes of Health (NIH); National Cancer Institute (NCI)
• Information provided by (Responsible Party): Catherine M. Bender, PhD, RN, FAAN, University of Pittsburgh

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Behavioral: Moderate-Intensity Aerobic Exercise Intervention	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 161 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Basic Science
• Official Title: Influence of Exercise on Neurocognitive Function in Breast Cancer
• Actual Study Start Date: April 2016
• Actual Primary Completion Date: January 10, 2023
• Actual Study Completion Date: January 10, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Moderate-intensity aerobic exercise; Participants engage in a supervised 6-month moderate-intensity aerobic exercise 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).
No Intervention: Usual Care; Physical activity neither limited nor withheld. Participants engage in activity in the same manner as if they were not part of an active intervention.

Outcome Measures

Primary Outcome Measures :

1. Change in cognitive function [ Time Frame: Baseline and 6 months ]
   A comprehensive neuropsychological battery to assess 6 domains of cognitive function (attention, learning and memory, executive function, mental flexibility, psychomotor efficiency, visuospatial ability)

Secondary Outcome Measures :

1. Neuroimaging metrics of brain health [ Time Frame: Baseline and 6 months ]
   fMRI will be used to measure regional gray matter volume, white matter architecture and functional dynamics of the brain.
2. Pro-inflammatory cytokines [ Time Frame: Baseline and 6 months ]
3. Cardiovascular Fitness (submaximal VO2) [ Time Frame: Baseline and 6 months ]
   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.
4. Energy expenditure (SenseWear physical activity-monitoring armband) [ Time Frame: Baseline, 3.5 months and 7 months ]
   Energy expenditure will be measured using SenseWear physical activity-monitoring armbands. This armband is worn around the upper arm (left triceps) for 1 week at a time.
5. Estradiol (E2) levels [ Time Frame: Baseline and 6 months ]
6. Fatigue [ Time Frame: Baseline and 6 months ]
   The Fatigue 8a Patient Reported Outcomes Measurement Information System (PROMIS) short form will be used to measure fatigue.
7. Anxiety [ Time Frame: Baseline and 6 months ]
   The Anxiety 8a PROMIS short form will be used to measure anxiety.
8. Sleep problems [ Time Frame: Baseline and 6 months ]
   Sleep problems will be measured using SenseWear physical activity-monitoring armband.
9. Sleep problems [ Time Frame: Baseline and 6 months ]
   Sleep problems will be measured using the Pittsburgh Sleep Quality Index.
10. Sleep problems [ Time Frame: Baseline and 6 months ]
    Sleep problems will be measured using the Epworth Sleepiness Scale.
11. Depressive symptoms [ Time Frame: Baseline and 6 months ]
    Depressive symptoms will be measured using the Beck Depression Inventory II.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15261

Sponsors and Collaborators

University of Pittsburgh

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Catherine M Bender, PhD; University of Pittsburgh
• Principal Investigator: Kirk I Erickson, PhD; University of Pittsburgh

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Catherine M. Bender, PhD, RN, FAAN, Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT02793921
• Other Study ID Numbers: R01CA196762 ( U.S. NIH Grant/Contract ); 1R01CA196762-01A1 ( U.S. NIH Grant/Contract )
• First Posted: June 8, 2016
• Last Update Posted: January 11, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: At the completion of the intervention, after investigators have been un-blinded to group status, and after the testing and publication of the primary aims and hypotheses, the investigators will provide de-identified data to interested investigators provided that they closely consult with Drs. Bender and Erickson with respect to study design, analytical procedures, and to avoid overlapping research in analyses or manuscript preparation. The primary investigative team will be given priority in addressing scientific questions of interest with the collected data, but will work closely with any interested investigators in maximizing the data to address other questions of interest that could be answered by these data.

Keywords provided by Catherine M. Bender, PhD, RN, FAAN, University of Pittsburgh:

Alteration; Cognitive Function; Exercise

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases