The Exercise and Familial Adenomatous Polyp (FAP) Study

Inclusion Criteria

• Individuals with FAP as defined by: * Genetic diagnosis: APC germline pathogenic variant (PV)/likely pathogenic variant (LPV) or obligate APC germline PV/LPV carrier (with or without family history), OR * Clinical diagnosis: A personal history of > 100 colorectal adenomas and a first degree relative with FAP or a personal history of colectomy for polyposis by age 39 and family history of FAP
• Have an intact rectum defined as status post colectomy and ileocolonic anastomosis for polyposis or pre-colectomy
• ≥ 5 rectal polyps > 2 mm in size on baseline lower endoscopy
• Participants must have no evidence of invasive cancer for 6 months prior to screening and must be at least 6 months from any prior cancer-directed treatment (such as surgical resection, chemotherapy, immunotherapy, hormonal therapy or radiation)
• No initiation of daily use of sulindac, celecoxib or other non-steroidal anti-inflammatory medications (NSAIDs) within 3 months of day 1 and no initiation > 25% of the time (> 8 days/month) for the duration of study participation
• No initiation of semaglutide, liraglutide (glucagon-like peptide-1 receptor agonist [GLP-1 receptor agonist]), tirzepatide (glucose-dependent insulinotropic polypeptide [GIP]), orlistat (lipase inhibitor) or other weight loss medications, within 3 months of day 1 and during study participation
• Adults ≥ 18 years of age
• Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Participants on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
• Lower endoscopy, required for participation in the study, is contraindicated in pregnancy. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and until after the end of study endoscopy is completed. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform the study team immediately
• Inactive defined as ≤ 90 minutes of moderate or strenuous exercise per week over the past month as assessed by the Godin Leisure Time Exercise Questionnaire
• Cleared for moderate-intensity exercise therapy using the Physical Activity Readiness Questionnaire (PAR-Q+) with screening clearance provided at the discretion of the local site principal investigator
• Sufficient space to house a treadmill in primary residence for the intervention period or access to an approved treadmill (as determined by study exercise physiologist) for the intervention period (e.g., participant may have access to a treadmill via an existing membership to a health club)
• Ability for study team to deliver and install exercise equipment in primary residence * Note: If participant will be using treadmill from another source approved by study exercise physiologist, this inclusion criteria is not applicable
• Internet or Wi-Fi connection. For participants without internet or Wi-Fi, a pre-paid cellular iPad will be provided
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
• Participant physician's approval
• Ability to understand and willingness to sign a written informed consent document in English. Given the extensive amount of verbal guidance from the study team required to perform each exercise therapy session (e.g., speed and incline of the treadmill, instructions on measurement of vital signs), extensive verbal feedback from the participant to the study team during each session (e.g., heart rate, symptoms), and the number of exercise therapy sessions over the course of the 24-week intervention, only those participants able to speak and comprehend English fluently are eligible

Exclusion Criteria

• History of total proctocolectomy
• Histologically-confirmed high-grade dysplasia or cancer on biopsy at screening
• History of pelvic radiation
• Participants receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of severe, progressive, or uncontrolled renal, genitourinary, hepatic, hematologic, endocrine, cardiac, vascular, pulmonary, rheumatologic, neurologic, psychiatric, or metabolic disturbances, or signs and symptoms thereof
• Pregnant women are excluded since endoscopy is not recommended while pregnant