Ursodeoxycholic Acid for C. diff Infection

(PREVENT Trial)

Overseen By Daniel Stein, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Medical College of Wisconsin

Must be taking: Antibiotics

Disqualifiers: Fulminant colitis, Liver disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding Ursodeoxycholic Acid (UDCA), a bile acid, to standard antibiotic treatment can prevent the recurrence of C. diff colitis, a common and serious gut infection. Researchers aim to determine if UDCA can prevent the infection's return, reduce the need for repeated antibiotics, and ensure its safety. Participants will be adults with a positive C. diff test who are already receiving standard antibiotic treatments. The trial will monitor UDCA's safety and effectiveness through regular check-ins and stool tests to track progress. If successful, this approach could reduce the chances of C. diff recurrence and lessen reliance on antibiotics. As an Early Phase 1 trial, this research focuses on understanding how UDCA works in people, offering participants a chance to contribute to groundbreaking treatment development.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you will continue your standard antibiotic treatment for C. diff while taking the study medication, UDCA.

Is there any evidence suggesting that Ursodeoxycholic Acid is likely to be safe for humans?

Research has shown that Ursodeoxycholic Acid (UDCA) is generally safe for people. The FDA has approved it, and it has been used for many years to treat liver problems and gallstones. Most people tolerate it well, though some may experience mild side effects like diarrhea, nausea, or an upset stomach.

In the case of C. diff infections, UDCA effectively stops the growth of the bacteria that cause these infections, potentially preventing the infection from returning.

As this is an early-stage study, the main goal is to learn more about how well people tolerate UDCA when used for C. diff infections. Researchers will closely monitor participants to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ursodeoxycholic Acid (UDCA) is unique because it offers a new approach to treating C. diff infections by potentially working alongside standard antibiotics like Flagyl, Vancomycin, or Fidaxomicin. While most treatments for C. diff target the bacteria directly, UDCA may help in restoring balance to the gut environment, which is often disrupted by the infection and antibiotics. Researchers are excited about UDCA because it has the potential to reduce infection recurrence and enhance overall gut health, making it a promising addition to current treatment options.

What evidence suggests that Ursodeoxycholic Acid might be an effective treatment for C. diff?

Research has shown that ursodeoxycholic acid (UDCA) might help prevent C. diff infections from recurring after treatment. Lab tests have found that UDCA stops C. diff from growing and spreading. It also reduces swelling in the gut, which could help the body fight off C. diff infections. Although more studies are needed, these early results suggest that UDCA could work well with antibiotics to lower the risk of C. diff returning. Participants in this trial will receive standard care treatment (Flagyl, Vancomycin, or Fidaxomicin) combined with UDCA to evaluate its effectiveness in preventing recurrence. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults with a positive C. diff test currently receiving standard antibiotics for C. diff colitis can join this trial. It's not for those with severe or life-threatening C. diff, serious liver disease, less than six months to live, or who are pregnant/breastfeeding.

Inclusion Criteria

I am over 18, tested positive for C. diff, and need treatment with specific antibiotics.

Exclusion Criteria

Life expectancy less than 6 months

My liver is not working properly.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive standard antibiotic treatment plus UDCA 500 mg three times a day for up to eight weeks

8 weeks

Weekly phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment, with stool tests at 4 and 8 weeks

3 months

2 visits (in-person) for stool testing

What Are the Treatments Tested in This Trial?

Interventions

• Ursodeoxycholic Acid (UDCA)

Trial Overview The study tests if Ursodeoxycholic Acid (UDCA) at 500 mg three times daily prevents the return of C. diff when taken with usual antibiotics like Vancomycin, Fidaxomicin, or Metronidazole over eight weeks.

How Is the Trial Designed?

Group I: UDCA Arm Experimental Treatment 1 Intervention

Standard of care treatment (Flagyl, Vancomycin or Fidaxomicin) + UDCA 500 mg TID for 8 weeks. UDCA to be started while patient is on antibiotics for C. difficile and continue for 8 weeks total.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

In a study involving 20 healthy dogs, 6-8 weeks of ursodeoxycholic acid (UDCA) administration significantly increased fasting serum bile acids (SBA) levels, but these levels remained within the normal reference range for most dogs.

UDCA treatment did not affect liver enzyme activities, bilirubin, cholesterol, or triglyceride concentrations, indicating that it is safe for long-term use in healthy dogs without causing adverse biochemical changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 6-8 weeks of oral ursodeoxycholic acid administration on serum concentrations of fasting and postprandial bile acids and biochemical analytes in healthy dogs. Deitz, KL., Makielski, KM., Williams, JM., et al.[2016]

In a study of 21 heart transplant recipients treated with ursodeoxycholic acid (UDCA) for cyclosporine-induced cholestasis, there was a significant reduction in acute rejection episodes compared to 31 control patients, with an average of 1.38 vs 2.74 episodes per patient.

The cumulative rejection severity score was also significantly lower in the UDCA group (2.38 vs 5.06), suggesting that UDCA may have beneficial immunomodulatory effects in the early phase after heart transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant treatment with ursodeoxycholic acid may reduce the incidence of acute cardiac allograft rejection. Bährle, S., Szabó, G., Stiehl, A., et al.[2013]

Ursodeoxycholic acid (UDCA) can be efficiently produced using a one-biocatalyst system with glucose dehydrogenase (GDH), achieving over 99.5% conversion of dehydrocholic acid (DHCA) to 12-keto-UDCA in just 4.5 hours on a liter scale.

This new method significantly improves the yield and efficiency of UDCA production compared to the traditional seven-step chemical process, which has an overall yield of less than 30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-enzymatic one-pot reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid with whole-cell biocatalysts. Sun, B., Kantzow, C., Bresch, S., et al.[2013]

Ursodeoxycholic acid (UDCA) effectively inhibits the germination and growth of Clostridium difficile in all tested strains, suggesting its potential as a nonantibiotic treatment for C. difficile-associated pouchitis.

A patient with recurrent C. difficile infection (RCDI) pouchitis, who was unresponsive to multiple antibiotics and fecal microbiota transplantation, remained infection-free for over 10 months after treatment with oral UDCA, indicating its promising therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection. Weingarden, AR., Chen, C., Zhang, N., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7240095/

Ursodeoxycholic Acid (UDCA) Mitigates the Host Inflammatory ... The highest concentration of ursodiol (7.64 mM) had a significant and immediate inhibitory effect on C. difficile viability compared to ethanol at time zero.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06884748?cond=%22Clostridioides%20difficile%22&aggFilters=status:not%20rec&rank=2

Prevention of Recurrence of Clostridioides Difficile Colitis ... ... Ursodeoxycholic Acid (UDCA) can help prevent recurrence of Clostridioides difficile (C. diff) colitis when used along with standard antibiotic treatment. C.

3. withpower.com withpower.com/trial/early-phase-1-clostridium-infections-4-2025-90613

Ursodeoxycholic Acid for C. diff Infection (PREVENT Trial) Ursodeoxycholic acid (UDCA) effectively inhibits the germination and growth of Clostridium difficile in all tested strains, suggesting its potential as a ...

4. news-medical.net news-medical.net/news/20200330/UDCA-treatment-affects-C-diff-life-cycle-reduces-inflammatory-response-in-mice.aspx

UDCA treatment affects C. diff life cycle, reduces ... (2020) Ursodeoxycholic acid (UDCA) mitigates the host inflammatory response during Clostridioides difficile infection by altering gut bile acids ...

5. biorxiv.org biorxiv.org/content/10.1101/2020.01.16.910018v1.full.pdf

Ursodeoxycholic acid (UDCA) mitigates the host ... Page 1. 1. Title: Ursodeoxycholic acid (UDCA) mitigates the host inflammatory response during. 1. Clostridioides difficile infection by altering ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1931312825000551

A designed synthetic microbiota provides insight to ... We designed a synthetic fecal microbiota transplant (sFMT1) by reconstructing microbial networks negatively associated with C. difficile colonization.

7. link.springer.com link.springer.com/article/10.1007/s40259-023-00617-2

Recurrent Clostridioides difficile Infection: Current Clinical ... The most common complication of C. difficile infection is recurrence, with rates of 20–30% after a primary infection and 60% after three or more episodes.