ROME: Gut Microbe Composition, Exercise, and Breast Breast Cancer Survivors

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Recruiting

CT.gov ID

NCT04088708

Collaborator

National Cancer Institute (NCI) (NIH)

126

Enrollment

Location

Arms

67.4

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Gut Microbiome Exercise Fatigue	Other: Aerobic Exercise Training Other: Attention Control	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

126 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized controlled trialRandomized controlled trial

Masking:

Single (Outcomes Assessor)

Masking Description:

Assessors will be blinded to participant study group allocation

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Jan 17, 2020

Anticipated Primary Completion Date :

Aug 31, 2025

Anticipated Study Completion Date :

Aug 31, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Composition of gut microbiota as measured by fecal samples [Baseline]
Using standard diversity and taxa comparison metrics
Composition of gut microbiota as measured by fecal samples [5 weeks after baseline]
Using standard diversity and taxa comparison metrics
Composition of gut microbiota as measured by fecal samples [10 weeks after baseline]
Using standard diversity and taxa comparison metrics
Composition of gut microbiota as measured by fecal samples [15 weeks after baseline]
Using standard diversity and taxa comparison metrics

Secondary Outcome Measures

Systemic inflammation tested via blood biomarkers [Baseline]
Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)
Systemic inflammation tested via blood biomarkers [5 weeks after baseline]
Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)
Systemic inflammation tested via biomarkers [10 weeks after baseline]
Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)
Systemic inflammation tested via blood biomarkers [15 weeks after baseline]
Blood samples will be analyzed for markers of inflammation (IL-6, IL-10)
Autonomic nervous system measured through non-invasive ECG [Baseline]
Using a Biopac MP 160 to measure heart rate variability and impedance cardiography while resting quietly
Autonomic nervous system measured through non-invasive ECG [5 weeks after baseline]
Using a Biopac MP 160 to measure heart rate variability and impedance cardiography while resting quietly
Autonomic nervous system measured through non-invasive ECG [10 weeks after baseline]
Using a Biopac MP 160 to measure heart rate variability and impedance cardiography while resting quietly
Autonomic nervous system measured through non-invasive ECG [15 weeks after baseline]
Using a Biopac MP 160 to measure heart rate variability and impedance cardiography while resting quietly
Concentration of cortisol measured through hair sample [Baseline]
Hormone change that is associated with stress
Concentration of cortisol measured through hair sample [5 weeks after baseline]
Hormone change that is associated with stress
Concentration of cortisol measured through hair sample [10 weeks after baseline]
Hormone change that is associated with stress
Concentration of cortisol measured through hair sample [15 weeks after baseline]
Hormone change that is associated with stress
Fatigue measured through fatigue specific questionnaire [Baseline]
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
Fatigue measured through fatigue specific questionnaire [5 weeks after baseline]
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
Fatigue measured through fatigue specific questionnaire [10 weeks after baseline]
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
Fatigue measured through fatigue specific questionnaire [15 weeks after baseline]
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

Other Outcome Measures

Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol [Baseline]
Cardiorespiratory fitness test on a treadmill
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol [5 weeks after baseline]
Cardiorespiratory fitness test on a treadmill
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol [10 weeks after baseline]
Cardiorespiratory fitness test on a treadmill
Peak VO2 (oxygen consumption) measured via modified Balke treadmill protocol [15 weeks after baseline]
Cardiorespiratory fitness test on a treadmill
Walking Economy measured via 6 minute treadmill test [Baseline]
Fitness test on a treadmill
Walking Economy measured via 6 minute treadmill test [5 weeks after baseline]
Fitness test on a treadmill
Walking Economy measured via 6 minute treadmill test [10 weeks after baseline]
Fitness test on a treadmill
Walking Economy measured via 6 minute treadmill test [15 weeks after baseline]
Fitness test on a treadmill
Accelerometer Measured Free-living physical activity (e.g., minutes of activity) [Baseline]
Motion sensor measures physical activity not observed during intervention activities
Accelerometer Measured Free-living physical activity (e.g., minutes of activity) [5 weeks after baseline]
Motion sensor measures physical activity not observed during intervention activities
Accelerometer Measured Free-living physical activity (e.g., minutes of activity) [10 weeks after baseline]
Motion sensor measures physical activity not observed during intervention activities
Accelerometer Measured Free-living physical activity (e.g., minutes of activity) [15 weeks after baseline]
Motion sensor measures physical activity not observed during intervention activities
Body composition using a dual energy x-ray absorptiometry [Baseline]
Measurement of body composition
Body composition using a dual energy x-ray absorptiometry [5 weeks after baseline]
Measurement of body composition
Body composition using a dual energy x-ray absorptiometry [10 weeks after baseline]
Measurement of body composition
Body composition using a dual energy x-ray absorptiometry [15 weeks after baseline]
Measurement of body composition
FACT-B self-administered survey measuring quality of life [Baseline]
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
FACT-B self-administered survey measuring quality of life [5 weeks after baseline]
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
FACT-B self-administered survey measuring quality of life [10 weeks after baseline]
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
FACT-B self-administered survey measuring quality of life [15 weeks after baseline]
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
Self-efficacy by self-administered survey [Baseline]
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.
Self-efficacy by self-administered survey [6 weeks after baseline]
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.
Self-efficacy by self-administered survey [10 weeks after baseline]
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.
Self-efficacy by self-administered survey [15 weeks after baseline]
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.
Self-administered survey measuring mood and stress [Baseline]
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.
Self-administered survey measuring mood and stress [5 weeks after baseline]
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.
Self-administered survey measuring mood and stress [10 weeks after baseline]
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.
Self-administered survey measuring mood and stress [15 weeks after baseline]
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.
Self-administered survey measuring memory [Baseline]
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.
Self-administered survey measuring memory [5 weeks after baseline]
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.
Self-administered survey measuring memory [10 weeks after baseline]
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.
Self-administered survey measuring memory [15 weeks after baseline]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion criteria:

Women ages 18 to 70 years with 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 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)
Participating, on average, in >30 minutes of exercise on ≥3 days per week during the past six months
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