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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Ursodeoxycholic Acid (UDCA) for C. diff infection?

Research suggests that Ursodeoxycholic Acid (UDCA) can inhibit the growth of Clostridium difficile, the bacteria responsible for C. diff infections, and may help prevent related conditions like ileal pouchitis. Additionally, UDCA has been shown to have various beneficial properties, such as protecting liver cells and dissolving gallstones, which indicate its broad therapeutic potential. ^{1 2 3 4 5}

Is ursodeoxycholic acid (UDCA) generally safe for humans?

Ursodeoxycholic acid (UDCA) is generally considered safe for treating certain liver conditions, with few side effects at standard doses. However, high doses have been linked to serious side effects, including liver damage and increased risk of liver cancer, especially in certain conditions like primary sclerosing cholangitis. ^{3 5 6 7 8}

How does the drug ursodeoxycholic acid differ from other treatments for C. diff infection?

Ursodeoxycholic acid (UDCA) is unique because it inhibits the growth of C. diff bacteria and prevents recurrence of related conditions, unlike standard antibiotics that only target active infections. It is a bile acid that also has protective effects on liver cells, making it different from typical treatments for C. diff. ^{1 3 4 5 6}

What is the purpose of this trial?

The goal of this clinical trial is to determine whether Ursodeoxycholic Acid (UDCA) can help prevent recurrence of Clostridioides difficile (C. diff) colitis when used along with standard antibiotic treatment. C. diff colitis is a serious infection that can return after treatment, and researchers want to see if UDCA can reduce this risk. This study aims to answer three main questions. First, can UDCA help prevent C. diff from returning after standard treatment? Second, does adding UDCA to treatment lower the need for repeated antibiotic use? Third, is UDCA safe and well-tolerated for people with C. diff? Participants in the study will be adults diagnosed with C. diff colitis who have risk factors for recurrence. Each participant will receive standard antibiotic treatment, which may include Vancomycin, Fidaxomicin, or Metronidazole. In addition to their antibiotic therapy, participants will take UDCA at a dose of 500 mg three times a day for up to eight weeks. If a participant's stool test shows they are C. diff negative at four weeks, they will stop taking UDCA early. Researchers will monitor participants throughout the study. Stool samples will be tested at the beginning, after four weeks, and at the end of the study. If a participant develops diarrhea, a stool test will check for C. diff. If C. diff is negative, the UDCA dose will be reduced. Weekly phone calls will be made to check for side effects and ensure participants are following the treatment plan. C. diff colitis is a common and serious infection, with up to 46 percent of high-risk patients experiencing recurrence. Current treatments rely on antibiotics, which can disrupt gut bacteria and increase the risk of reinfection. UDCA is a naturally occurring bile acid that may help prevent C. diff from growing, reducing the need for repeated antibiotic treatment. If successful, this study could introduce a new way to prevent C. diff from coming back, helping patients recover more effectively while reducing antibiotic use. Eligible participants must be at least 18 years old, have a positive C. diff test, and be receiving standard antibiotic treatment for C. diff. People who have severe or life-threatening C. diff colitis, a life expectancy of less than six months, serious liver disease, or are pregnant or breastfeeding will not be eligible to participate. UDCA is FDA-approved and has been used safely for decades in liver diseases and gallstone treatment. Some people may experience mild side effects, such as diarrhea, nausea, or stomach discomfort. Participants will be closely monitored for safety throughout the study. This trial will take place within the Froedtert and Medical College of Wisconsin healthcare system in Milwaukee, Wisconsin.

Eligibility Criteria

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

I am not pregnant or breastfeeding.

I am unable to understand and agree to the study's procedures and risks.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Multi-enzymatic one-pot reduction of dehydrocholic acid to 12-keto-ursodeoxycholic acid with whole-cell biocatalysts. [2013]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Ursodeoxycholic acid: A therapeutic niche in an internist's practice]. [2018]

3. United States 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. [2020]

4. United States 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. [2016]

5. Poland pubmed.ncbi.nlm.nih.gov

[Clinical pharmacology of ursodeoxycholic acid (UDCA)]. [2013]

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

Adjuvant treatment with ursodeoxycholic acid may reduce the incidence of acute cardiac allograft rejection. [2013]

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

Molecular mechanisms of ursodeoxycholic acid toxicity & side effects: ursodeoxycholic acid freezes regeneration & induces hibernation mode. [2022]

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

A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. [2022]