Gut Microbe Composition, Exercise, and Breast Breast Cancer Survivors (ROME)

Role of Gut Microbe Composition in Psychosocial Symptom Response to Exercise Training in Breast Cancer Survivors (ROME Study)

The primary goal of this project is to determine the effects of exercise on the gut microbiome in breast cancer survivors and determine how these changes may relate to psychosocial symptoms such as fatigue.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Fatigue; Exercise; Gut Microbiome
• Intervention / Treatment: Other: Aerobic Exercise Training; Other: Attention Control

Detailed Description

Cancer survivors are at increased risk of gut bacteria communities that can negatively impact health and energy level and it is possible that exercise can cause healthy changes in these communities. Through careful design, this study will use a controlled-feeding diet and 10 weeks of exercise training to determine exercise effects on the number, distribution, and types of bacteria in the gut of breast cancer survivors. These changes will then be linked to fatigue and physiologic effects of exercise to determine how the information can be used to enhance exercise benefits and identify new treatment strategies leveraging changes in gut bacteria communities.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Q Rogers, MD, MPH; Phone Number: 2059349735 (205) - 934 - 9735; Email: rogersl@uab.edu
• Study Contact Backup: Name: Ildiko Nyikos, M.A., ACSM-RCEP; Phone Number: (205) - 975-0002; Email: inyikos@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-001
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Laura Q Rogers, MD, MPH; Phone Number: (205) 934-9735; Email: rogersl@uab.edu
      • Contact: Ildiko Nyikos, M.A., ACSM-RCEP; Phone Number: 2059750002; Email: inyikos@uabmc.edu
      • Principal Investigator: Laura Q Rogers, MD
      • Sub-Investigator: Gary Hunter, PhD
      • Sub-Investigator: Bulent Turan, PhD
      • Sub-Investigator: Helen Krontiras, MD
      • Sub-Investigator: Elliot Lefkowitz, PhD
      • Sub-Investigator: Robert Motl, PhD
      • Sub-Investigator: Nianjun Liu, PhD
      • Sub-Investigator: Stephen J Carter, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Women ages 18 to 74 years with a history of breast cancer stage 0, I, II, or III,
• ≥ 1-year post-completion of primary treatment for breast cancer (chemotherapy and/or radiation),
• Average fatigue over the past week rated as ≥3 on a 1 to 10 Likert scale, cut point chosen because it is a clinically meaningful cutpoint,93
• English speaking,
• Physician medical clearance for study participation,
• Able to ambulate without assistance,
• No antibiotics for the past 90 days,
• Willing to avoid taking probiotics for the duration of the study
• Peak VO2 <30 ml/kg/min (note: will measure peak VO2 if the participant meets all other criteria and consents to lab-based screening).

Exclusion criteria:

• Metastatic or recurrent cancer
• Another diagnosis of cancer in the past 5 years (not including skin or cervical cancer in situ), 3)
• Unstable angina
• New York Heart Association class II, III, or IV congestive heart failure
• Uncontrolled asthma
• Interstitial lung disease
• Current steroid use
• Having been told by a physician to only do exercise prescribed by a physician
• Dementia or organic brain syndrome
• Schizophrenia or active psychosis
• Connective tissue or rheumatologic disease (i.e., systemic lupus erythematosus, rheumatoid arthritis, amyloidosis, Reiter's syndrome, psoriatic arthritis, mixed connective tissue disease, Sjögren's syndrome, CREST syndrome, polymyositis, dermatomyositis, progressive systemic sclerosis, vasculitis, polymyalgia rheumatic, temporal arteritis)
• Anticipate elective surgery during the study period
• Anticipate changes in usual medications during the study period
• Plan to move residence out of the local area during the study period
• Plan to travel out of the local area for >1 week during study participation
• Contraindication to engaging in moderate-to-vigorous intensity aerobic exercise
• Currently pregnant or anticipate pregnancy during study participation
• Live or work >50 miles from study site or do not have transportation to study site
• BMI >50
• Anticipate needing antibiotics during the study period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Exercise Training; Progressive aerobic exercise training sessions supervised by exercise specialists who have experience training cancer survivors.	Other: Aerobic Exercise Training; Each session will last 20 to 60 minutes depending on the stage of progression (shorter duration in the first few weeks). Sessions will occur on nonconsecutive days of the week. Moderate-intensity, continuous aerobic exercise will be used to target large muscle groups (e.g., legs) with the principal goal of increasing cardiorespiratory fitness. Exercise intensity will be gradually increased. To mitigate stagnation and support continued improvement of cardiorespiratory fitness, high-intensity interval exercise will be added in later weeks of the intervention.
Active Comparator: Attention Control; The non-aerobic exercise attention control condition will control for the effects of attention with flexibility/toning activities.	Other: Attention Control; The flexibility/toning control condition will be delivered using the same frequency as the aerobic condition (i.e., 3 times per week) and use light resistance bands of least difficulty. The flexibility/toning sessions will last about 40 minutes, be led by trained exercise specialists. Flexibility/toning activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, and ankle/foot. The progression of activities over the 10-week period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands (i.e., Thera-bands) that provide minimal resistance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of gut microbiota as measured by fecal samples	Using standard diversity and taxa comparison metrics	Baseline
Composition of gut microbiota as measured by fecal samples	Using standard diversity and taxa comparison metrics	5 weeks after baseline
Composition of gut microbiota as measured by fecal samples	Using standard diversity and taxa comparison metrics	10 weeks after baseline
Composition of gut microbiota as measured by fecal samples	Using standard diversity and taxa comparison metrics	15 weeks after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic inflammation tested via blood biomarkers	Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)	Baseline
Systemic inflammation tested via blood biomarkers	Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)	5 weeks after baseline
Systemic inflammation tested via biomarkers	Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)	10 weeks after baseline
Systemic inflammation tested via blood biomarkers	Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)	15 weeks after baseline
Concentration of cortisol measured through hair sample	Hormone change that is associated with stress	Baseline
Concentration of cortisol measured through hair sample	Hormone change that is associated with stress	5 weeks after baseline
Concentration of cortisol measured through hair sample	Hormone change that is associated with stress	10 weeks after baseline
Concentration of cortisol measured through hair sample	Hormone change that is associated with stress	15 weeks after baseline
Fatigue measured through fatigue specific questionnaire	Fatigue Symptom Inventory which contains 13 items (fatigue intensity = mean of 4 items, 1 to 10 scale; fatigue interference = mean of 7 items, 0 to 10 scale; 2 general fatigue items = 0 to 7 scale and 1 to 10 scale); higher score indicates greater fatigue	Baseline
Fatigue measured through fatigue specific questionnaire	Fatigue Symptom Inventory which contains 13 items (fatigue intensity = mean of 4 items, 1 to 10 scale; fatigue interference = mean of 7 items, 0 to 10 scale; 2 general fatigue items = 0 to 7 scale and 1 to 10 scale); higher score indicates greater fatigue	5 weeks after baseline
Fatigue measured through fatigue specific questionnaire	Fatigue Symptom Inventory which contains 13 items (fatigue intensity = mean of 4 items, 1 to 10 scale; fatigue interference = mean of 7 items, 0 to 10 scale; 2 general fatigue items = 0 to 7 scale and 1 to 10 scale); higher score indicates greater fatigue	10 weeks after baseline
Fatigue measured through fatigue specific questionnaire	Fatigue Symptom Inventory which contains 13 items (fatigue intensity = mean of 4 items, 1 to 10 scale; fatigue interference = mean of 7 items, 0 to 10 scale; 2 general fatigue items = 0 to 7 scale and 1 to 10 scale); higher score indicates greater fatigue	15 weeks after baseline
Autonomic nervous system measured through non-invasive ECG	Using a Actiheart 5 to measure heart rate variability and impedance cardiography while resting quietly	Baseline
Autonomic nervous system measured through non-invasive ECG	Using a Actiheart 5 to measure heart rate variability and impedance cardiography while resting quietly	5 weeks after baseline
Autonomic nervous system measured through non-invasive ECG	Using a Actiheart 5 to measure heart rate variability and impedance cardiography while resting quietly	10 weeks after baseline
Autonomic nervous system measured through non-invasive ECG	Using a Actiheart 5 to measure heart rate variability and impedance cardiography while resting quietly	15 weeks after baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol	Cardiorespiratory fitness test on a treadmill	Baseline
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol	Cardiorespiratory fitness test on a treadmill	5 weeks after baseline
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol	Cardiorespiratory fitness test on a treadmill	10 weeks after baseline
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol	Cardiorespiratory fitness test on a treadmill	15 weeks after baseline
Walking Economy measured via 6 minute treadmill test	Fitness test on a treadmill	Baseline
Walking Economy measured via 6 minute treadmill test	Fitness test on a treadmill	5 weeks after baseline
Walking Economy measured via 6 minute treadmill test	Fitness test on a treadmill	10 weeks after baseline
Walking Economy measured via 6 minute treadmill test	Fitness test on a treadmill	15 weeks after baseline
Accelerometer Measured Free-living physical activity (e.g., minutes of activity)	Motion sensor measures physical activity not observed during intervention activities	Baseline
Accelerometer Measured Free-living physical activity (e.g., minutes of activity)	Motion sensor measures physical activity not observed during intervention activities	5 weeks after baseline
Accelerometer Measured Free-living physical activity (e.g., minutes of activity)	Motion sensor measures physical activity not observed during intervention activities	10 weeks after baseline
Accelerometer Measured Free-living physical activity (e.g., minutes of activity)	Motion sensor measures physical activity not observed during intervention activities	15 weeks after baseline
Body composition using a dual energy x-ray absorptiometry	Measurement of body composition	Baseline
Body composition using a dual energy x-ray absorptiometry	Measurement of body composition	5 weeks after baseline
Body composition using a dual energy x-ray absorptiometry	Measurement of body composition	10 weeks after baseline
Body composition using a dual energy x-ray absorptiometry	Measurement of body composition	15 weeks after baseline
FACT-B self-administered survey measuring quality of life	Functional Assessment of Cancer Therapy (FACT) - Breast quality of life scale (37 items; 0 to 4 scale; range is 0 to 148); higher score indicates better quality of life	Baseline
FACT-B self-administered survey measuring quality of life	Functional Assessment of Cancer Therapy (FACT) - Breast quality of life scale (37 items; 0 to 4 scale; range is 0 to 148); higher score indicates better quality of life	5 weeks after baseline
FACT-B self-administered survey measuring quality of life	Functional Assessment of Cancer Therapy (FACT) - Breast quality of life scale (37 items; 0 to 4 scale; range is 0 to 148); higher score indicates better quality of life	10 weeks after baseline
FACT-B self-administered survey measuring quality of life	Functional Assessment of Cancer Therapy (FACT) - Breast quality of life scale (37 items; 0 to 4 scale; range is 0 to 148); higher score indicates better quality of life	15 weeks after baseline
Self-efficacy by self-administered survey	Self-efficacy measured with 15 items (barriers self-efficacy = 9 items and walking self-efficacy = 6 items, mean of 0% to 100% Scale, range is 0% to 100%); higher score indicates higher self-efficacy.	Baseline
Self-efficacy by self-administered survey	Self-efficacy measured with 15 items (barriers self-efficacy = 9 items and walking self-efficacy = 6 items, mean of 0% to 100% Scale, range is 0% to 100%); higher score indicates higher self-efficacy.	6 weeks after baseline
Self-efficacy by self-administered survey	Self-efficacy measured with 15 items (barriers self-efficacy = 9 items and walking self-efficacy = 6 items, mean of 0% to 100% Scale, range is 0% to 100%); higher score indicates higher self-efficacy.	10 weeks after baseline
Self-efficacy by self-administered survey	Self-efficacy measured with 15 items (barriers self-efficacy = 9 items and walking self-efficacy = 6 items, mean of 0% to 100% Scale, range is 0% to 100%); higher score indicates higher self-efficacy.	15 weeks after baseline
Self-administered survey measuring mood and stress	Measurement of mood and stress after a traumatic experience, Civilian PTSD ( total of 17 items, 1 to 5 scale; range of 17 to 85) higher scores indicate greater PTSD. Perceived Stress Scale - 10 (10 items, 1 to 5 scale; 10 to 50 range) higher score indicates greater perceived stress.	Baseline
Self-administered survey measuring mood and stress	Measurement of mood and stress after a traumatic experience, Civilian PTSD ( total of 17 items, 1 to 5 scale; range of 17 to 85) higher scores indicate greater PTSD. Perceived Stress Scale - 10 (10 items, 1 to 5 scale; 10 to 50 range) higher score indicates greater perceived stress.	5 weeks after baseline
Self-administered survey measuring mood and stress	Measurement of mood and stress after a traumatic experience, Civilian PTSD ( total of 17 items, 1 to 5 scale; range of 17 to 85) higher scores indicate greater PTSD. Perceived Stress Scale - 10 (10 items, 1 to 5 scale; 10 to 50 range) higher score indicates greater perceived stress.	10 weeks after baseline
Self-administered survey measuring mood and stress	Measurement of mood and stress after a traumatic experience, Civilian PTSD ( total of 17 items, 1 to 5 scale; range of 17 to 85) higher scores indicate greater PTSD. Perceived Stress Scale - 10 (10 items, 1 to 5 scale; 10 to 50 range) higher score indicates greater perceived stress.	15 weeks after baseline
Self-administered survey measuring memory	Measurement of memory through frequency of forgetting scale (total of 10 items, 1 to 7 scale; range of 10 to 70) higher score indicate lower frequency of forgetting and higher level of memory.	Baseline
Self-administered survey measuring memory	Measurement of memory through frequency of forgetting scale (total of 10 items, 1 to 7 scale; range of 10 to 70) higher score indicate lower frequency of forgetting and higher level of memory.	5 weeks after baseline
Self-administered survey measuring memory	Measurement of memory through frequency of forgetting scale (total of 10 items, 1 to 7 scale; range of 10 to 70) higher score indicate lower frequency of forgetting and higher level of memory.	10 weeks after baseline
Self-administered survey measuring memory	Measurement of memory through frequency of forgetting scale (total of 10 items, 1 to 7 scale; range of 10 to 70) higher score indicate lower frequency of forgetting and higher level of memory.	15 weeks after baseline

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Laura Q Rogers, MD, MPH, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: August 3, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; fatigue; exercise; inflammation; gut microbiome; psychosocial outcomes
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Fatigue
• Other Study ID Numbers: IRB-30000320; R01CA235598 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Any data collected with National Institutes of Health (NIH) funding and made public through publication in a peer-reviewed format will thereafter be available on request to faculty of institutions with Public Health Service (PHS) assurance. For sharing data and specimens from individual human subjects, the investigators will comply with all relevant policies including the "Standards for Privacy of Individually Identifiable Health Information" rule of the Health Insurance Portability and Accountability Act (HIPAA). For sharing data, the investigators will comply with the requirements of the Final NIH Statement on Sharing Research Data (NOT-OD-03-032), the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies (GWAS) (NOT-OD-07-088), the NIH Genomic Data Sharing Policy (NOT-OD-14-124), and all other existing, updated, and new requirements as stated by NIH policy.
• IPD Sharing Time Frame: To be determined
• IPD Sharing Access Criteria: To be determined
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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