Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis

Part A

Inclusion Criteria:

1. Have a diagnosis of FAP with genetic testing demonstrating a pathogenic or likelypathogenic germline variant in APC, must have a clinical FAP phenotype with at leastone member of the family who has a pathogenic or likely pathogenic germline variantin APC, or must have a clinical diagnosis of FAP as agreed by two gastrointestinalcancer genetics experts

2. Must have an extensive colonic resection with either a subtotal colectomy withileorectal anastomosis (STC-IRA) or total proctocolectomy with ileal pouch analanastomosis (TPC-IPAA)

3. Can provide informed consent

Exclusion Criteria:

1. Subject is pregnant, a prisoner, or is under 18 years of age

2. Prior total proctocolectomy with end ileostomy

3. History of inflammatory bowel disease

4. History of diabetes mellitus and are currently on medical diabetes therapy

5. History of chronic kidney disease with an eGFR < 60 mL/min/1.73m2

6. Cancer diagnosis where the subject is receiving active therapy

7. Use of either a ketogenic diet or intermittent fasting (defined as a fasting periodof 16 hours or more per day that is not associated with a medical procedure) duringthe 4 weeks prior to enrollment

Part B

Inclusion Criteria:

1. Have a diagnosis of FAP with genetic testing demonstrating a pathogenic or likelypathogenic germline variant in APC, must have a clinical FAP phenotype with at leastone member of the family who has a pathogenic or likely pathogenic germline variantin APC, or must have a clinical diagnosis of FAP as agreed by two gastrointestinalcancer genetics experts.

2. Willing to undergo a colonoscopy or sigmoidoscopy, which may be part of thepatient's routine standard care.

3. Able to have a concurrent upper endoscopy performed with thecolonoscopy/sigmoidoscopy. This upper endoscopy may be part of the patient's routinestandard care.

4. Have at least two colorectal polyps at enrollment (which can be present anywhere inthe colon including the rectal cuff, or in the J-pouch [if applicable]).

5. Can provide informed consent.

Exclusion Criteria:

1. Subject is pregnant, a prisoner, or is under 18 years of age

2. Patient is not able to undergo colonoscopy/sigmoidoscopy or upper endoscopy

3. Prior total proctocolectomy with end ileostomy

4. History of inflammatory bowel disease

5. History of diabetes mellitus and are currently on medical diabetes therapy

6. History of chronic kidney disease with an eGFR < 60 mL/min/1.73m2

7. Cancer diagnosis where the subject is receiving active therapy

8. Use of either a ketogenic diet or intermittent fasting (defined as a fasting periodof 16 hours or more per day that is not associated with a medical procedure) duringthe 4 weeks prior to enrollment

9. Regular use of any FAP-related chemopreventive agent in the 6 weeks prior toenrollment including aspirin (> 81mg daily), NSAIDs, BHB supplementation, or anyother medication deemed a chemopreventive agent by the study investigators

10. Any colonic or small intestinal polyp observed endoscopically that is > 1 cm in sizeand is not removed (excluding ampullary adenomas)