FAPBHB-FAPNCT06578637
Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis
A study testing R-1,3-Butanediol (10G-A), R-1,3-Butanediol (20G-A) and R-1,3-Butanediol (30G-A) in people with FAP and Familial Adenomatous Polyposis, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- FAP, Familial Adenomatous Polyposis
- What is being tested?
- R-1,3-Butanediol (10G-A), R-1,3-Butanediol (20G-A) and R-1,3-Butanediol (30G-A)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Sep 2024to Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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.
- Willing to undergo a colonoscopy or sigmoidoscopy, which may be part of the patient's routine standard care.
- 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.
- 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]).
- Can provide informed consent.
Who cannot join
- 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
Show all 18Show fewer
- 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
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this 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.
Read the 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.
- Conditions
- FAP, Familial Adenomatous Polyposis
- Being tested
- R-1,3-Butanediol (10G-A), R-1,3-Butanediol (20G-A), R-1,3-Butanediol (30G-A), R-1,3-Butanediol (30G-B)
- Keywords
- FAP, Familial adenomatous polyposis, Chemoprevention, Polyps, BHB, Beta-hydroxybutyrate
- Medical subject headings
- Adenomatous Polyposis Coli, Polyps
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
R-1,3-Butanediol (10G-A)Dietary supplement
Also called HVMN Ketone-IQ
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
R-1,3-Butanediol (20G-A)Dietary supplement
Also called HVMN Ketone-IQ
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
R-1,3-Butanediol (30G-A)Dietary supplement
Also called HVMN Ketone-IQ
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
R-1,3-Butanediol (30G-B)Dietary supplement
Also called HVMN Ketone-IQ
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
| Study group | Role | What they receive |
|---|---|---|
| Part A - 10 grams | Experimental | 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 Receives: Dietary Supplement: R-1,3-Butanediol (10G-A) |
| Part A - 20 grams | Experimental | 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 Receives: Dietary Supplement: R-1,3-Butanediol (20G-A) |
| Part A - 30 grams | Experimental | 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 Receives: Dietary Supplement: R-1,3-Butanediol (30G-A) |
| Part B - 30 grams | Experimental | 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 Receives: Dietary Supplement: R-1,3-Butanediol (30G-B) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Through study completion, which will be approximately 3 years
Secondary outcomes (3)
Measure whether oral BHB supplementations increases serum BHB levels in FAP
Measure fasting serum BHB levels before, during, and at the end of BHB supplementation to determine if BHB supplementation significantly increases serum BHB levels.
Measured: 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
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.
Measured: Through study completion, which will be approximately 3 years
Determine whether oral BHB supplementation in FAP reduces intestinal polyp burden
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.
Measured: Through study completion, which will be approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2024
- Study start20 Sep 2024
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FAPStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The V Foundation for Cancer Research
- Responsible party
- Sponsor
- Investigators
- Bryson W Katona, MD, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06578637
- Sponsor's protocol ID
- UPCC 08224
- Acronym
- BHB-FAP
- Status last verified
- Sep 2026
- First submitted
- 27 Aug 2024
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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 35477756
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis
- ClinicalTrials.gov ID
- NCT06578637
- Acronym / sponsor ID
- BHB-FAP / UPCC 08224
- Conditions
- FAP, Familial Adenomatous Polyposis
- Keywords
- FAP, Familial adenomatous polyposis, Chemoprevention, Polyps, BHB, Beta-hydroxybutyrate
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- The V Foundation for Cancer Research
- Study start
- 20 Sep 2024 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 29 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A - 10 grams | Experimental | Dietary Supplement: R-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 |
| Part A - 20 grams | Experimental | Dietary Supplement: R-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 |
| Part A - 30 grams | Experimental | Dietary Supplement: R-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 |
| Part B - 30 grams | Experimental | Dietary Supplement: R-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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
- 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.
- Willing to undergo a colonoscopy or sigmoidoscopy, which may be part of the patient's routine standard care.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| R-1,3-Butanediol (10G-A)Also: HVMN Ketone-IQStudy 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 supplement | Part A - 10 grams |
| R-1,3-Butanediol (20G-A)Also: HVMN Ketone-IQStudy 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 supplement | Part A - 20 grams |
| R-1,3-Butanediol (30G-A)Also: HVMN Ketone-IQStudy 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 supplement | Part A - 30 grams |
| R-1,3-Butanediol (30G-B)Also: HVMN Ketone-IQStudy 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 | Dietary supplement | Part B - 30 grams |
Primary outcome
Determine whether oral BHB supplementation is safe and tolerable in FAP
Time frame: 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.
3 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
- Results publication: PubMed 35477756Dmitrieva-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bryson W Katona, MD, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing R-1,3-Butanediol (10G-A), R-1,3-Butanediol (20G-A) and R-1,3-Butanediol (30G-A) in people with FAP and Familial Adenomatous Polyposis, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine whether oral BHB supplementation is safe and tolerable in FAP (time frame: Through study completion, which will be approximately 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06578637, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.