Trial of Exercise Therapy in Familial Adenomatous Polyp (FAP)

Inclusion Criteria:

* Individuals with FAP as defined by:

  * Genetic diagnosis: APC germline mutation (with or without FAP family history), OR
  * Clinical diagnosis: FAP phenotype with a history of more than 50 colorectal adenomas
* 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 ≤ 60 minutes of moderate or strenuous exercise per week over the past month as assessed by the Godin Leisure Time Exercise Questionnaire
* No self-reported contraindications to regular exercise as evaluated by the Physical Activity Readiness Questionnaire (PAR-Q+)
* 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
* Physician approval
* Ability to understand and willingness to sign a written informed consent document

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