Beta-Hydroxybutyrate for Crohn's Disease

(BHB Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Linda Feagins

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Texas at Austin

Must not be taking: Antibiotics, Acid suppressors, Probiotics

Disqualifiers: Ketogenic diet, Intermittent fasting, C. difficile, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This clinical trial aims to understand the feasibility of patients taking ketone body supplement beta-hydroxybutyrate (BHB) for 4 weeks with a confirmed diagnosis of Crohn's disease and starting new therapy for active disease. The main questions it aims to answer are: * BHB supplementation will be feasible and acceptable to patients. * BHB supplementation will be associated with a reduction in systemic inflammation. * BHB supplementation will be associated with a reduction in pro-inflammatory bacterial colonies. Participants will: * Take 3 capsules x 3 times per day for 4 weeks. * Document food consumption using a 24-hour food recall questionnaire. * Provide blood and fecal samples twice, at the beginning of the study and the 4-week mark. Researchers will compare the group taking the ketone body supplement and the group not taking the supplement to see if the supplement provides relief of symptoms suffered from Crohn's disease.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are starting a new therapy for Crohn's disease. If you are using certain supplements or diets, like BHB supplements, a ketogenic diet, or intermittent fasting, you must stop those before joining.

What evidence supports the effectiveness of the treatment Beta-Hydroxybutyrate for Crohn's Disease?

Research suggests that certain fatty acids, like n-3 polyunsaturated fatty acids, may influence the activity of Crohn's disease, although results are mixed. While Beta-Hydroxybutyrate itself isn't directly studied, the role of fatty acids in inflammation and Crohn's disease suggests potential benefits. ^{1 2 3 4 5}

Is Beta-Hydroxybutyrate safe for humans?

Research on Beta-Hydroxybutyrate (3HB) suggests it is generally safe as it has been used in studies to prevent colonic inflammation and improve gut health in mice. It has shown potential in treating inflammatory bowel diseases by promoting beneficial gut bacteria and reducing inflammation. ^{6 7 8 9 10}

How is the treatment Beta-Hydroxybutyrate unique for Crohn's Disease?

Beta-Hydroxybutyrate (BHB) is unique for Crohn's Disease as it acts as a ketone body that can improve gut health by altering the gut microbiome and reducing inflammation. Unlike traditional treatments, BHB can be administered as a food supplement or through engineered probiotics, offering a novel approach to managing inflammation and promoting a healthy gut environment. ^{6 8 9 11 12}

Research Team

Linda Feagins

Principal Investigator

University of Texas at Austin

Eligibility Criteria

This trial is for individuals with Crohn's Disease or Irritable Bowel Syndrome who are starting new treatments. Participants will take a ketone body supplement, beta-hydroxybutyrate (BHB), and must be willing to document their food intake and provide blood and fecal samples at the start and end of the 4-week study.

Inclusion Criteria

Managed at UT Digestive Health Clinic

I am starting a new treatment involving specific targeted drugs.

I am 18 years old or older.

Exclusion Criteria

Unwilling to provide signed consent

Currently or recently (within 4 weeks) following a ketogenic diet

I have not taken antibiotics in the last 3 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take beta-hydroxybutyrate (BHB) supplements for 4 weeks, documenting food consumption and providing blood and fecal samples.

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and disease activity.

4 weeks

Long-term Follow-up

Assessment of patient adherence to the intervention and ability to enroll patients within the target timeframe.

12 months

Treatment Details

Interventions

• Beta-Hydroxybutyrate (Ketone Body Supplement)

Trial Overview The study tests if taking BHB supplements three times daily for four weeks can make it easier for patients to manage Crohn's disease by reducing inflammation and pro-inflammatory bacteria in the gut compared to those not taking the supplement.

Participant Groups

Group I: Standard of care therapy plus BHB supplementation (intervention). Active Control 1 Intervention

Arm does receives the BHB supplement

Group II: standard of care therapy (control) Active Control 1 Intervention

Arm does not receive the BHB supplement

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Dr. Elly Barry

University of Texas at Austin

Chief Medical Officer

MD from Harvard Medical School

Dr. Brian Windsor

University of Texas at Austin

Chief Executive Officer since 2023

PhD in Molecular Biology from the University of Texas at Austin

Findings from Research

Neutralizing antibodies against TNF-alpha have been confirmed to play a significant role in Crohn's disease, highlighting the importance of cytokines in the disease's pathophysiology.

While n-3 fatty acids showed some potential benefits in ulcerative colitis, including significant improvements in clinical activity in some studies, their overall efficacy remains inconclusive, particularly in Crohn's disease, with mixed results from various trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid treatment of inflammatory bowel disease. Endres, S., Lorenz, R., Loeschke, K.[2019]

In a study of 36 patients with Crohn's disease who had undergone ileal resection, it was found that they had lower levels of unsaturated fatty acids in their blood compared to healthy individuals, indicating a potential deficiency in these important nutrients.

Despite the lower blood levels, the patients had higher proportions of unsaturated fatty acids in their adipose tissue, suggesting that their bodies may be compensating for this deficiency due to an increased demand for fatty acid precursors needed for prostaglandin synthesis in the remaining bowel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatty acid composition in serum lipids and adipose tissue in patients with morbus Crohn after ileal resection. Johansson, C., Walldius, G., Rössner, S.[2018]

In a study of 20 patients with Crohn's disease, serum levels of certain fatty acids, particularly n3 polyunsaturated fatty acids, were found to be significantly lower compared to 18 healthy controls, indicating a potential deficiency in these beneficial fats.

The research suggests that while essential fatty acids are generally not deficient in Crohn's disease, lower levels of n3 polyunsaturated fatty acids may correlate with disease activity, highlighting their possible role in managing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum n3 polyunsaturated fatty acids are depleted in Crohn's disease. Kuroki, F., Iida, M., Matsumoto, T., et al.[2019]

Dietary changes, such as increasing calorie intake and fiber or using total parenteral nutrition, can be effective as primary treatments for Crohn's disease, suggesting that nutrition plays a crucial role in managing this condition.

Eicosapentaenoic acid may have therapeutic potential for ulcerative colitis by competing with arachidonic acid and reducing inflammation, although this is based on a small pilot study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional therapy in ambulatory patients. O'Morain, CA.[2020]

The study developed pH-responsive nanoparticles (CSA-PENPs) using biosynthesized polyhydroxybutyrate (PHB) and Eudragit FS, which effectively targeted drug delivery to inflamed tissues in a murine model of colitis.

CSA-PENPs demonstrated enhanced therapeutic efficacy by providing sustained release of cyclosporine A (CSA) directly to the affected areas, leading to significant anti-inflammatory effects compared to conventional CSA-loaded nanoparticles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cupriavidus necator-Produced Polyhydroxybutyrate/Eudragit FS Hybrid Nanoparticles Mitigates Ulcerative Colitis via Colon-Targeted Delivery of Cyclosporine A. Lee, J., Saparbayeva, A., Hlaing, SP., et al.[2022]

Poly-D-3-hydroxybutyric acid (PHB) can be degraded by intestinal microbiota, acting as a slow-release source of 3-hydroxybutyrate (3-HB), which is beneficial in suppressing inflammation in models of inflammatory bowel disease (IBD).

In a study using a dextran sulfate sodium-induced IBD model, a PHB diet not only increased 3-HB levels in feces and blood but also reduced weight loss and inflammation, while promoting regulatory T cell accumulation in the rectum, suggesting its potential as a treatment for IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The novel sustained 3-hydroxybutyrate donor poly-D-3-hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T-cells. Suzuki, R., Mishima, M., Nagane, M., et al.[2023]

The study identified that gut bacteria, particularly from the Proteobacteria and Firmicutes phyla, are capable of producing 2-hydroxybutyric acid (2HB), with Fusobacterium nucleatum being the most effective at synthesizing it.

Despite the presence of 2HB-producing bacteria in the gut, the research found that these bacteria have a limited impact on serum 2HB levels, indicating that while they contribute to intestinal 2HB concentrations, they do not significantly influence circulating 2HB in the bloodstream.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo. Qin, F., Li, J., Mao, T., et al.[2023]

Exogenous β-hydroxybutyrate (BHB) and a ketogenic diet (KD) significantly reduced disease activity and improved colon health in rats with dextran sodium sulfate (DSS)-induced ulcerative colitis, indicating their potential as therapeutic interventions.

Both BHB and KD effectively inhibited the NLRP3 inflammasome activation and reduced inflammatory markers, suggesting they not only alleviate symptoms of ulcerative colitis but also promote healing of the intestinal barrier and restore microbiota balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis. Abdelhady, R., Saber, S., Ahmed Abdel-Reheim, M., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Essential fatty acid status in paediatric Crohn's disease: relationship with disease activity and nutritional status. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Lipid treatment of inflammatory bowel disease. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Fatty acid composition in serum lipids and adipose tissue in patients with morbus Crohn after ileal resection. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Serum n3 polyunsaturated fatty acids are depleted in Crohn's disease. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Nutritional therapy in ambulatory patients. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Applications and Mechanism of 3-Hydroxybutyrate (3HB) for Prevention of Colonic Inflammation and Carcinogenesis as a Food Supplement. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cupriavidus necator-Produced Polyhydroxybutyrate/Eudragit FS Hybrid Nanoparticles Mitigates Ulcerative Colitis via Colon-Targeted Delivery of Cyclosporine A. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

The novel sustained 3-hydroxybutyrate donor poly-D-3-hydroxybutyric acid prevents inflammatory bowel disease through upregulation of regulatory T-cells. [2023]

9. China pubmed.ncbi.nlm.nih.gov

Construction of a sustainable 3-hydroxybutyrate-producing probiotic Escherichia coli for treatment of colitis. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

New prebiotics by ketone donation. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis. [2023]