Investigation of β-hydroxybutyrate Supplementation as Chemoprevention in Familial Adenomatous Polyposis (BHB-FAP)

August 27, 2025 updated by: Abramson Cancer Center at Penn Medicine
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Abramson Cancer Center of the University of Pennsylvania
        • Contact:
        • Principal Investigator:
          • Bryson W Katona, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A - 10 grams
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 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
Other Names:
  • HVMN Ketone-IQ
Experimental: Part A - 20 grams
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 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
Other Names:
  • HVMN Ketone-IQ
Experimental: Part A - 30 grams
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 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
Other Names:
  • HVMN Ketone-IQ
Experimental: Part B - 30 grams
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
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
Other Names:
  • HVMN Ketone-IQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through study completion, which will be approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure whether oral BHB supplementations increases serum BHB levels in FAP
Time Frame: 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.
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
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.
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
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.
Through study completion, which will be approximately 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abramson Cancer Center at Penn Medicine

Collaborators

The V Foundation for Cancer Research

Investigators

  • Principal Investigator: Bryson W Katona, MD, PhD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2024

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

August 27, 2024

First Submitted That Met QC Criteria

August 28, 2024

First Posted (Actual)

August 29, 2024

Study Record Updates

Last Update Posted (Estimated)

September 4, 2025

Last Update Submitted That Met QC Criteria

August 27, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 08224

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Familial Adenomatous Polyposis

Clinical Trials on R-1,3-Butanediol (10G-A)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe