Evaluating the Effects of an Exercise Intervention on the Gut Microbiota in Stage II-III Colorectal Cancer Survivors

Study Overview
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Brief Summary
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This trial evaluates the effects a moderate-to-vigorous exercise intervention has on the bacterial make-up of the gastrointestinal tract (gut microbiota) in survivors of stage II-III colorectal cancer (CRC). Data shows that the gut microbiota composition and function may be drivers of CRC. High levels of exercise are associated with improved CRC prognosis and survival. While data suggests that exercise has the potential to influence gut microbiota composition and function, it is not known whether these effects contribute to improved CRC prognosis. This clinical trial evaluates the effects an exercise intervention has on gut microbiota and how these effects relate to CRC progression and patient-reported outcomes.

Detailed Description
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OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive the supervised exercise intervention over 8 weeks on study. Patients also undergo collection of blood samples at baseline and week 8. ARM B: Patients receive health-related information for 8 weeks on study. Patients are then offered a session of supervised exercise followed by 7 weeks of tele-coaching sessions. Patients also undergo collection of blood samples at baseline and week 8.

Official Title
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A Randomized Controlled Trial Testing the Effects of an Exercise Intervention on the Gut Microbiota in Colorectal Cancer Survivors: A Pilot and Feasibility Study

Conditions
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Stage II Colorectal Cancer AJCC v8, Stage III Colorectal Cancer AJCC v8

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Other: Exercise Intervention
* Other: Exercise Intervention
* Behavioral: Health Education
* Other: Interview
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years of age Previous diagnosis of stage II-III CRC cancer No known recurrent or metastatic disease No comorbid or physical limitations that would limit participation at the discretion of the treating provider At least 60 days to 3 years from last cancer-directed treatment (including surgery, chemotherapy, and radiation. Elective surgery, including ileostomy reversal, is not counted in this timing but patients must be able to eat a normal diet, without post-operative dietary limitations) Body mass index (BMI) 18.5-30 kg/m^2 Able to understand and willing to sign written informed consent in English Access to phone for study contacts Be willing and able to attend the 24 sessions at the Fred Hutch Exercise Research Center Shared Resource Access to smartphone Willingness to participate in all study activities Completion of all run-in activities Participants must not be active smokers within the past 30 days. Active smoking is defined as any smoking, even a puff. Participants who smoke are much less likely to engage in healthy lifestyle behaviors, and it is probably more important for participants to stop smoking than it is to change their exercise patterns. If identified as a smoker, the individual will be referred to the local resources, Washington State Quitline (1-800-QUIT-NOW), ICanQuit.org, Quit2Heal.org, the national resource, Centers for Disease Control and Prevention (CDC) Quit Now phone line which supports smoking cessation, or the National Institutes of Health (NIH) quit support website SmokeFree.gov At time of consent, participants must engage =< 60 minutes per week of moderate to vigorous physical activity, as assessed by brief questionnaires at screening and then objectively assessed using accelerometers at baseline Participants must have an Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status score of 0 or 1 for performance status Physician approval for participation in an 8-week exercise program Women must not be pregnant at time of enrollment Exclusion Criteria: Use of oral or intravenous antibiotics, antifungals, or antiparasitics during the past 6 months Presence of an ileostomy or colostomy because of known changes to the gut microbiome with ileostomies and colostomies Current status of underweight (BMI < 18.5 kg/m^2) or obese (BMI 30.0 kg/m^2) Presence of inflammatory bowel diseases such as Crohn's disease or ulcerative colitis as these are known to baseline have differences in gut microbiome composition Active smokers within the past 30 days Women who are pregnant or breastfeeding, or planning to become pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (exercise intervention)<br>Patients receive the supervised exercise intervention over 8 weeks on study. Patients also undergo collection of blood samples at baseline and week 8. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Other: Exercise Intervention<br>* Receive exercise intervention<br>Other: Interview<br>* Ancillary studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm B (waitlist control)<br>Patients receive health-related information for 8 weeks on study. Patients are then offered a session of supervised exercise followed by 7 weeks of tele-coaching sessions. Patients also undergo collection of blood samples at baseline and week 8. | Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Other: Exercise Intervention<br>* Receive tele-coaching intervention<br>Behavioral: Health Education<br>* Receive health-related information<br>Other: Interview<br>* Ancillary studies<br>Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment | Recruitment (accrual rate) will be assessed to determine feasibility. Will be summarized using descriptive statistics. | Up to 8 weeks | 
| Adherence | Adherence will be measured by session attendance in the intervention arm to determine feasibility. Will be summarized using descriptive statistics. | Up to 8 weeks | 
| Retention | Retention will be measured by completion of all study assessments, including physical activity via accelerometry, 24 hour dietary recalls, and completion of the follow-up data collection at 8 weeks to determine feasibility. Will be summarized using descriptive statistics. Statistical differences in retention rates for each study assessment between study arms will be assessed by logistic regression models and acceptability by linear regression models, with models adjusted for stratification factors. | Up to 8 weeks | 
| Acceptability | Acceptability will be measured on a Likert scale in each of a series of questions regarding various aspects of the trial during the exit interview to determine feasibility. Will be summarized using descriptive statistics. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of an 8 week supervised exercise intervention on fecal concentrations of butyrate | Will be summarized using descriptive statistics, and statistical differences between study arms will be assessed via linear regression models with adjustment for baseline outcome values and stratification factors. | At 8 weeks | 
| Effects of an 8 week supervised exercise intervention on fecal concentrations of other short chain fatty acids | Will be summarized using descriptive statistics, and statistical differences between study arms will be assessed via linear regression models with adjustment for baseline outcome values and stratification factors. | At 8 weeks |