Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis
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 potentially reducing the need for frequent upper endoscopies and colonoscopies and 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 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.
Arms & interventions
- Dietary SupplementR-1,3-Butanediol (10G-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
- Dietary SupplementR-1,3-Butanediol (20G-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
- Dietary SupplementR-1,3-Butanediol (30G-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
- Dietary SupplementR-1,3-Butanediol (30G-B)
Study participants will take one 35mL dose of HVMN Ketone-IQ by mouth three times per day (30 total grams of R-1,3-Butanediol) for 12 weeks, with a possible additional 12 week extension
Outcome measures
Primary
Determine whether oral BHB supplementation is safe and tolerable in FAP
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.
Time frame: Through study completion, which will be approximately 3 years
Secondary
Measure whether oral BHB supplementations increases serum BHB levels in FAP
Time frame: Through study completion, which will be approximately 3 years
Change in transcription and protein expression in the intestinal mucosa and in intestinal polyps in FAP after oral BHB supplementation
Time frame: Through study completion, which will be approximately 3 years
Determine whether oral BHB supplementation in FAP reduces intestinal polyp burden
Time frame: Through study completion, which will be approximately 3 years
Eligibility criteria
Study locations (1)
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
References
- Dmitrieva-Posocco O, Wong AC, Lundgren P, Golos AM, Descamps HC, Dohnalova L, Cramer Z, Tian Y, Yueh B, Eskiocak O, Egervari G, Lan Y, Liu J, Fan J, Kim J, Madhu B, Schneider KM, Khoziainova S, Andreeva N, Wang Q, Li N, Furth EE, Bailis W, Kelsen JR, Hamilton KE, Kaestner KH, Berger SL, Epstein JA, Jain R, Li M, Beyaz S, Lengner CJ, Katona BW, Grivennikov SI, Thaiss CA, Levy M. beta-Hydroxybutyrate suppresses colorectal cancer. Nature. 2022 May;605(7908):160-165. doi: 10.1038/s41586-022-04649-6. Epub 2022 Apr 27.(PubMed)