Gut Microbe Composition, Exercise, and Breast Breast Cancer Survivors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Gut Microbiome, Exercise, Fatigue

Intervention / Treatment
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* Other: Aerobic Exercise Training
* Other: Attention Control


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Exercise Training<br>Progressive aerobic exercise training sessions supervised by exercise specialists who have experience training cancer survivors. | Other: Aerobic Exercise Training<br>* 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.<br>|
| Active Comparator: Attention Control<br>The non-aerobic exercise attention control condition will control for the effects of attention with flexibility/toning activities. | Other: Attention Control<br>* 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.<br>|

What is the study measuring?
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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 | 
| Autonomic nervous system measured through non-invasive ECG | Using a Biopac MP 160 to measure heart rate variability and impedance cardiography while resting quietly | Baseline | 
| Autonomic nervous system measured through non-invasive ECG | Using a Biopac MP 160 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 Biopac MP 160 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 Biopac MP 160 to measure heart rate variability and impedance cardiography while resting quietly | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, fatigue, exercise, psychosocial outcomes, inflammation, gut microbiome