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

Launched by ABRAMSON CANCER CENTER AT PENN MEDICINE · Aug 28, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating whether a supplement called β-hydroxybutyrate (BHB) can help prevent the growth of intestinal polyps in people with Familial Adenomatous Polyposis (FAP), a genetic condition that increases the risk of colorectal cancer. By potentially slowing down the development of these polyps, the study aims to reduce the number of regular endoscopies (procedures to examine the digestive tract) and possibly avoid the need for surgery in the future.

To participate, individuals must have a confirmed diagnosis of FAP and have undergone specific surgeries related to their condition. They should also be able to give consent to join the study. However, there are certain criteria that would exclude someone from participating, such as being pregnant, having certain health issues like diabetes or kidney disease, or using specific diets or medications related to polyps in the weeks leading up to the trial. If eligible, participants can expect to contribute to important research that might improve care for others with FAP.

Gender

ALL

Eligibility criteria

• • Part A
• Inclusion Criteria:
• • 1. Have a diagnosis of FAP with genetic testing demonstrating a pathogenic or likely pathogenic germline variant in APC, must have a clinical FAP phenotype with at least one member of the family who has a pathogenic or likely pathogenic germline variant in APC, or must have a clinical diagnosis of FAP as agreed by two gastrointestinal cancer genetics experts
• • 2. Must have an extensive colonic resection with either a subtotal colectomy with ileorectal anastomosis (STC-IRA) or total proctocolectomy with ileal pouch anal anastomosis (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 period of 16 hours or more per day that is not associated with a medical procedure) during the 4 weeks prior to enrollment
• • Part B
• Inclusion Criteria:
• • 1. Have a diagnosis of FAP with genetic testing demonstrating a pathogenic or likely pathogenic germline variant in APC, must have a clinical FAP phenotype with at least one member of the family who has a pathogenic or likely pathogenic germline variant in APC, or must have a clinical diagnosis of FAP as agreed by two gastrointestinal cancer genetics experts.
• • 2. Willing to undergo a colonoscopy or sigmoidoscopy, which may be part of the patient's routine standard care.
• • 3. Able to have a concurrent upper endoscopy performed with the colonoscopy/sigmoidoscopy. This upper endoscopy may be part of the patient's routine standard care.
• • 4. Have at least two colorectal polyps at enrollment (which can be present anywhere in the 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 period of 16 hours or more per day that is not associated with a medical procedure) during the 4 weeks prior to enrollment
• • 9. Regular use of any FAP-related chemopreventive agent in the 6 weeks prior to enrollment including aspirin (\> 81mg daily), NSAIDs, BHB supplementation, or any other medication deemed a chemopreventive agent by the study investigators
• • 10. Any colonic or small intestinal polyp observed endoscopically that is \> 1 cm in size and is not removed (excluding ampullary adenomas)