Association Between Changes in the Gut Microbiome and Chemotherapy-Induced Nausea in Stage I-III Breast Cancer

Study Overview
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Brief Summary
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This pilot study seeks to understand how changes in the bacteria composition (microbiome) of the gut may be associated with the occurrence of chemotherapy-induced nausea (CIN) in women undergoing chemotherapy for stage I-III breast cancer. Patients undergoing chemotherapy may experience nausea as a result of their treatment. Known risk factors for CIN do not explain the differences in CIN occurrence between patients, but changes in the functions of the gut microbiome may be related to the occurrence of CIN. This study collects stool samples from breast cancer patients before and after chemotherapy to evaluate how changes in the microbiome may be associated with CIN.

Detailed Description
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PRIMARY OBJECTIVES: I. Evaluate the feasibility of patient recruitment and retention, as well as specimen collection. II. Estimate the effect size for changes in gut microbiome composition profiles and metabolites in stool as well as blood from T1 to T2 that are associated with the occurrence of CIN. III. Evaluate associations between patient reported demographic and clinical characteristics, comorbidities at T1, and changes in gastrointestinal and neuropsychological symptoms, food intake as well as exercise from T1 to T2 with the occurrence of CIN. OUTLINE: Patients undergo collection of stool and blood samples and complete questionnaires at baseline and 3-5 days following initiation of standard of care chemotherapy.

Official Title
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A Pilot Study of the Associations Between Chemotherapy-Induced Nausea in Breast Cancer Patients and Gut Microbiome Composition Profiles

Conditions
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Chemotherapy-Related Nausea and/or Vomiting, Early Stage Breast Carcinoma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of early stage breast cancer, planning to receive moderate to highly emetogenic chemotherapy will be recruited at Mayo Clinic, Arizona and Mayo Clinic Florida At least 20 years of age Last chemotherapy more than 3 years ago Scheduled to receive moderate to highly emetogenic chemotherapy with or without targeted therapies including immunotherapies Exclusion Criteria: Metastatic disease Concurrent radiation therapy Concurrent antibiotic treatment

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational (survey, biospecimen collection)<br>Patients undergo collection of stool samples over 10 minutes and complete questionnaires over 60 minutes at baseline and 3-5 days following initiation of standard of care chemotherapy. | Procedure: Biospecimen Collection<br>* Undergo collection of stool and blood samples<br>* Other names: Specimen Collection;Other: Questionnaire Administration<br>* Complete questionnaires<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients approached | Assessed using descriptive statistics. | Up to 24 months | 
| Number of patients enrolled | Assessed using descriptive statistics. | Up to 24 months | 
| Number of patients who completed the questionnaires at both assessments | Assessed using descriptive statistics. | At baseline and 3-5 days after initiation of chemotherapy | 
| Number of patients who provided stool samples at both assessments | Assessed using descriptive statistics. | At baseline and 3-5 days after initiation of chemotherapy | 
| Bacterial composition of stool samples | All stool samples will be processed for deoxyribonucleic acid extraction. The hypervariable regions V3 and V4 of the bacterial 16S ribosomal ribonucleic acid (rRNA) gene will be sequenced to determine bacterial composition. After quality control, 16S rRNA reads will be analyzed to determine operational taxonomic units (OTU) for T1 and T2 samples using QIIME software. Alpha (within sample) diversity and beta (between sample) diversity will be analyzed using nonmetric multidimensional scaling ordination and the effect size for changes in OTUs in gut microbiome composition profiles from T1 to T2 in patients who do and do not report chemotherapy-induced nausea (CIN) at T2 as measured by questionnaire, will be determined using linear discriminant analysis effect size. | Up to study completion | 
| Differences in demographic between patients who do and do not report CIN | Evaluated using parametric and non-parametric tests. The changes in gastrointestinal and neuropsychological symptoms, food intake as well as exercise from T1 to T2 associated with the occurrence of CIN will be evaluated using Kruskal-Wallis tests. | Up to study completion | 
| Differences in clinical characteristics between patients who do and do not report CIN | Evaluated using parametric and non-parametric tests. The changes in gastrointestinal and neuropsychological symptoms, food intake as well as exercise from T1 to T2 associated with the occurrence of CIN will be evaluated using Kruskal-Wallis tests. | Up to study completion | 
| Differences in comorbidities between patients who do and do not report CIN | Evaluated using parametric and non-parametric tests. The changes in gastrointestinal and neuropsychological symptoms, food intake as well as exercise from T1 to T2 associated with the occurrence of CIN will be evaluated using Kruskal-Wallis tests. | Up to study completion |