Trial Title:
Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis
NCT ID:
NCT06578637
Condition:
FAP
Familial Adenomatous Polyposis
Conditions: Official terms:
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Adenomatous Polyposis Coli
Conditions: Keywords:
FAP
Familial adenomatous polyposis
Chemoprevention
Polyps
BHB
Beta-hydroxybutyrate
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Prevention
Masking:
Single (Participant)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
R-1,3-Butanediol (10MG-A)
Description:
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
Arm group label:
Part A - 10 grams
Other name:
HVMN Ketone-IQ
Intervention type:
Dietary Supplement
Intervention name:
R-1,3-Butanediol (20MG-A)
Description:
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
Arm group label:
Part A - 20 grams
Other name:
HVMN Ketone-IQ
Intervention type:
Dietary Supplement
Intervention name:
R-1,3-Butanediol (30MG-A)
Description:
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
Arm group label:
Part A - 30 grams
Other name:
HVMN Ketone-IQ
Intervention type:
Dietary Supplement
Intervention name:
R-1,3-Butanediol (10MG-B)
Description:
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
Arm group label:
Part B - 10 grams
Other name:
HVMN Ketone-IQ
Intervention type:
Dietary Supplement
Intervention name:
R-1,3-Butanediol (20MG-B)
Description:
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
Arm group label:
Part B - 20 grams
Other name:
HVMN Ketone-IQ
Intervention type:
Dietary Supplement
Intervention name:
Placebo
Description:
Study participants will take one 35mL dose of placebo ketone drink by mouth twice daily
for 12 weeks
Arm group label:
Part B - Placebo
Other name:
HVMN Ketone-IQ Placebo
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.
Criteria for eligibility:
Criteria:
Part A
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
- 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
Exclusion Criteria:
- 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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Abramson Cancer Center of the University of Pennsylvania
Address:
City:
Philadelphia
Zip:
19104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bryson W Katona, MD, PhD
Phone:
215-349-8222
Email:
bryson.katona@pennmedicine.upenn.edu
Investigator:
Last name:
Bryson W Katona, MD, PhD
Email:
Principal Investigator
Start date:
September 20, 2024
Completion date:
October 2027
Lead sponsor:
Agency:
Abramson Cancer Center at Penn Medicine
Agency class:
Other
Collaborator:
Agency:
The V Foundation for Cancer Research
Agency class:
Other
Source:
Abramson Cancer Center at Penn Medicine
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06578637
