Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis
- Conditions
- FAPFamilial Adenomatous Polyposis
- Interventions
- Dietary Supplement: R-1,3-Butanediol (30MG-A)Dietary Supplement: PlaceboDietary Supplement: R-1,3-Butanediol (10MG-A)Dietary Supplement: R-1,3-Butanediol (20MG-B)Dietary Supplement: R-1,3-Butanediol (20MG-A)Dietary Supplement: R-1,3-Butanediol (10MG-B)
- Registration Number
- NCT06578637
- Lead Sponsor
- Abramson Cancer Center at Penn Medicine
- Brief Summary
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 reducing the need for frequent upper endoscopies and colonoscopies, and potentially preventing the need for risk-reducing surgical intervention.
- Detailed Description
We plan to undertake both an initial absorption study (Part A) in up to 9 individuals with FAP followed by a longitudinal, randomized, placebo-controlled study (Part B) in 30 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 who undergo their scheduled colonoscopy/sigmoidoscopy along with an upper endoscopy will be consented and subsequently randomized to receive either placebo (10 individuals) or R-1,3-butanediol at one of two doses (20 individuals). The participants then return every 4 weeks for a blood draw and at that time will also provide a stool sample, which will allow us to monitor the levels of BHB in their systemic circulation and stool. 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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
- 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)
- Can provide informed consent
- Subject is pregnant, a prisoner, or is under 18 years of age
- Prior total proctocolectomy with end ileostomy
- History of inflammatory bowel disease
- History of diabetes mellitus and are currently on medical diabetes therapy
- History of chronic kidney disease with an eGFR < 60 mL/min/1.73m2
- Cancer diagnosis where the subject is receiving active therapy
- 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:
- 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.
- Scheduled for a colonoscopy or sigmoidoscopy as part of the patient's standard care
- Able to have a concurrent upper endoscopy performed with the standard of care colonoscopy/sigmoidoscopy
- Have at least two colorectal polyps (which can be present anywhere in the colon including the rectal cuff, or in the J-pouch [if applicable])
- Can provide informed consent
Exclusion Criteria:
- Subject is pregnant, a prisoner, or is under 18 years of age
- Patient is not able to undergo colonoscopy/sigmoidoscopy or upper endoscopy
- Prior total proctocolectomy with end ileostomy
- History of inflammatory bowel disease
- History of diabetes mellitus and are currently on medical diabetes therapy
- History of chronic kidney disease with an eGFR < 60 mL/min/1.73m2
- Cancer diagnosis where the subject is receiving active therapy
- 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
- 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
- Any colonic or small intestinal polyp observed endoscopically that is > 1 cm in size and is not removed (excluding ampullary adenomas)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part A - 30 grams R-1,3-Butanediol (30MG-A) Study participants will take three 35mL dose of HVMN Ketone-IQ by mouth per day (30 total grams of R-1,3-Butanediol) for 2 weeks Part B - Placebo Placebo Study participants will take one 35mL dose of placebo ketone drink by mouth twice daily for 12 weeks Part A - 10 grams R-1,3-Butanediol (10MG-A) Study participants will take one 35mL dose of HVMN Ketone-IQ by mouth per day (10 total grams of R-1,3-Butanediol) for 2 weeks Part B - 20 grams R-1,3-Butanediol (20MG-B) Study participants will take one 35mL dose of HVMN Ketone-IQ by mouth twice per day (20 total grams of R-1,3-Butanediol) for 12 weeks Part A - 20 grams R-1,3-Butanediol (20MG-A) Study participants will take two 35mL dose of HVMN Ketone-IQ by mouth per day (20 total grams of R-1,3-Butanediol) for 2 weeks Part B - 10 grams R-1,3-Butanediol (10MG-B) Study participants will take one 35mL dose of HVMN Ketone-IQ by mouth per day along with one 35mL dose of placebo ketone drink by mouth per day (10 total grams of R-1,3-Butanediol) for 12 weeks
- Primary Outcome Measures
Name Time Method Determine whether oral BHB supplementation is safe and tolerable in FAP Through study completion, which will be approximately 3 years Assessment of FAP patient tolerance of BHB supplements through monitoring of side effects and/or intolerances and patient compliance. We will monitor the percentage of individuals who continue BHB supplementation for the duration of the study, as well as the compliance with taking the BHB supplement.
- Secondary Outcome Measures
Name Time Method Measure whether oral BHB supplementations increases serum BHB levels in FAP Through study completion, which will be approximately 3 years Measure fasting serum BHB levels before, during, and at the end of BHB supplementation to determine if BHB supplementation significantly increases serum BHB levels.
Determine whether oral BHB supplementation in FAP reduces intestinal polyp burden Through study completion, which will be approximately 3 years The polyp burden in the duodenum as well as in the lower GI tract (rectal cuff, rectum, rectal pouch) will be calculated through polyp counting and measurement on endoscopy before and after BHB supplementation to permit comparison of polyp burden before and after BHB supplementation.
Change in transcription and protein expression in the intestinal mucosa and in intestinal polyps in FAP after oral BHB supplementation Through study completion, which will be approximately 3 years Transcriptional profiling and subsequent validation with protein level determination will be performed in the intestinal mucosa and in intestinal polyps before and after BHB supplementation to determine if BHB supplementation is having measurable transcriptional and protein effects on the intestinal mucosa and on intestinal polyps.
Trial Locations
- Locations (1)
Abramson Cancer Center of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States