Personalized home treadmill exercise for people with Familial Adenomatous Polyposis (FAP)

Phase 1a/b Trial of Exercise Therapy in Familial Adenomatous Polyp (FAP)

This trial will try different amounts of home treadmill exercise in people with FAP who have at least five rectal polyps to see if exercise can help prevent polyps from coming back.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Michigan Rogel Cancer Center (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 2 sites (Ann Arbor, Michigan and 1 other locations)
• Trial ID: NCT06641310 on ClinicalTrials.gov

What this trial studies

This phase 1a/b trial tests four different personalized treadmill exercise regimens delivered at home for 26 weeks. A treadmill will be placed in each participant's home and exercise sessions will be remotely monitored by exercise staff, with regimen intensity tailored to each person. Participants have baseline and 26-week in-person visits timed with standard endoscopy care, with small rectal biopsies, blood and stool samples, and questionnaires collected before and after the intervention. Results will inform the design of larger trials to determine whether exercise can reduce polyp recurrence in people with FAP.

Who should consider this trial

Good fit: People with a genetic APC mutation or clinical FAP (more than 50 colorectal adenomas) who have an intact rectum and at least five rectal polyps >2 mm, no recent invasive cancer or recent cancer-directed treatment, and who can safely perform treadmill exercise.

Not a fit: People without an intact rectum, with fewer than five rectal polyps, with recent invasive cancer or cancer treatment, or who cannot safely use a treadmill are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this could provide a low-risk, non-drug way to lower polyp recurrence and potentially reduce colorectal cancer risk in people with FAP.

How similar studies have performed: Exercise interventions have shown health benefits in other populations, but this personalized home treadmill approach is largely novel for preventing polyp recurrence in FAP and has not been proven.

Eligibility criteria

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

Where this trial is running

Ann Arbor, Michigan and 1 other locations

• University of Michigan Rogel Cancer Center — Ann Arbor, Michigan, United States (RECRUITING)
• Cleveland Clinic Foundation — Cleveland, Ohio, United States (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Samara Rifkin, MD — University of Michigan Rogel Cancer Center

Conditions: Familial Adenomatous Polyposis