Using β-hydroxybutyrate to prevent intestinal polyps in patients with Familial Adenomatous Polyposis

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

This study is testing if taking β-hydroxybutyrate can help prevent intestinal polyps in people with Familial Adenomatous Polyposis.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Abramson Cancer Center at Penn Medicine (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06578637 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of β-hydroxybutyrate (BHB) supplementation as a new approach to prevent the development and progression of intestinal adenomas in individuals diagnosed with Familial Adenomatous Polyposis (FAP). It consists of two parts: an initial absorption study involving 9 participants to assess BHB absorption, followed by a randomized, placebo-controlled study with 30 participants receiving varying doses of R-1,3-butanediol, a BHB precursor. Participants will undergo regular blood and stool sample collections to monitor BHB levels and will have endoscopic procedures to assess polyp development after 12 weeks of supplementation.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals diagnosed with Familial Adenomatous Polyposis who have undergone specific types of colonic surgery and can provide informed consent.

Not a fit: Patients who are pregnant, under 18 years of age, or have certain medical histories such as inflammatory bowel disease or chronic kidney disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the frequency of invasive procedures like colonoscopies and potentially prevent the need for surgical interventions in patients with FAP.

How similar studies have performed: While the use of BHB supplementation in this context is novel, similar studies exploring chemoprevention strategies in FAP have shown promise, indicating potential for success.

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)

Where this trial is running

Philadelphia, Pennsylvania

• Abramson Cancer Center of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Bryson W Katona, MD, PhD — University of Pennsylvania
• Study coordinator: Bryson W Katona, MD, PhD

Conditions FAP; Familial Adenomatous Polyposis; Familial adenomatous polyposis; Chemoprevention; Polyps; BHB; Beta-hydroxybutyrate