UPCC 08224 Investigation of β-hydroxybutyrate supplementation as chemoprevention in familial adenomatous polyposis (BHB-FAP) (BHB-FAP)

Study of Investigational Supplementation for Hereditary Colon Polyp Condition

Enrolling By Invitation
18 years or above
All
Phase N/A
20 participants needed
1 Location

Brief description of study

The aim of this study is to evaluate the potential of BHB supplementation as a novel strategy to impede the development and progression of intestinal adenomas in individuals with FAP, thus potentially reducing the need for frequent upper endoscopies and colonoscopies and preventing the need for risk-reducing surgical intervention.

Detailed description of study

We plan to undertake both an initial absorption study (Part A) in up to 9 individuals with FAP followed by a longitudinal open-label study (Part B) in up to 20 individuals with FAP, who will receive R-1,3-butanediol (HVMN Ketone-IQ), an orally administered BHB precursor. Participants with FAP in Part A will have a blood sample collected and then take R-1,3-butanediol at one of three different doses for 2 weeks, which will be followed by another blood sample collection. In Part B, participants with FAP will undergo colonoscopy/sigmoidoscopy along with an upper endoscopy and will then receive R-1,3-butanediol. The participants will return at 4 weeks and 8 weeks for a blood draw and at that time will also provide a stool sample, and participants will check their ketone levels at home weekly. After 12 weeks of R-1,3-butanediol consumption, an upper endoscopy and colonoscopy/sigmoidoscopy will be performed, which will be the same as the procedure performed on study entry. At this point participants can be finished with the study, or they may have the option of continuing BHB for another 12 weeks in an extension study, followed by a repeat upper endoscopy and colonoscopy/sigmoidoscopy at 24 weeks.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: FAP, Familial Adenomatous Polyposis
  • Age: 18 years or above
  • Gender: All

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)

This study investigates the use of investigational supplementation as a potential strategy to slow down the development and growth of intestinal adenomas in individuals with Familial Adenomatous Polyposis (FAP). The study aims to explore whether this supplementation can reduce the frequency of medical procedures like endoscopies and possibly delay the need for surgical interventions.

Participants in the study will undergo specific procedures to assess the effects of the investigational supplementation. Initially, a blood sample will be taken, followed by a period of taking the supplement at varying doses. Subsequent blood samples will be collected to monitor the body's response. In another phase, participants will have a colonoscopy and endoscopy, provide stool samples, and monitor ketone levels at home. These procedures are designed to evaluate the supplement's impact on polyp development and overall intestinal health.

  • Who can participate: Participants must have a diagnosis of FAP confirmed by genetic testing or clinical evaluation. They should be willing to undergo colonoscopy and endoscopy procedures. Individuals under 18, pregnant, or with certain medical conditions such as diabetes or chronic kidney disease are excluded.
  • Study details: Participants will take the investigational supplementation and undergo medical procedures such as blood draws, colonoscopies, and endoscopies. They will also monitor their ketone levels at home. The study may involve an extension phase with additional supplementation and procedures.
  • Study timelines and visits: The study will last 12 weeks. The study requires 3 visits.
Updated on 04 Sep 2025. Study ID: 24-0909
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