Ursodeoxycholic Acid for Pouchitis

Overseen By Sidhartha Sinha, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Stanford University

Must not be taking: NSAIDs, Immunosuppressants, Biologicals, others

Disqualifiers: Pregnancy, Allergy to UDCA, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 10 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ursodeoxycholic acid (UDCA) can reduce inflammation and improve quality of life in individuals with pouchitis, a condition often affecting those with inflammatory bowel disease (IBD) who have undergone colon removal surgery. The trial seeks to determine if UDCA can help when antibiotics are ineffective or required continuously. Suitable candidates for this trial have had surgery for ulcerative colitis, experience frequent stools, and continue to have pouch inflammation despite antibiotic treatments. As a Phase 2 trial, this research measures UDCA's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial allows participants to stay on stable doses of certain medications for pouchitis, like oral 5-ASA, oral steroids (below specific doses), and immunosuppressants. However, changes in these medications close to the trial start are not allowed, and some medications must be stopped weeks before joining. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ursodeoxycholic acid (UDCA) is likely to be safe for humans?

Research has shown that ursodeoxycholic acid (UDCA) may help with certain types of inflammation in the colon. Studies have found that it can improve symptoms by affecting specific inflammatory processes. A higher dose appears more effective at reducing inflammation.

Real-world data has identified common side effects of UDCA, such as diarrhea or loose stools, which are typical for this drug. In terms of safety evidence, the trial is in later stages, indicating that UDCA is generally well-tolerated. While side effects can occur, not everyone experiences them. Discuss potential risks and benefits with a healthcare provider when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment for pouchitis, which usually relies on antibiotics, Ursodeoxycholic Acid (UDCA) offers a novel approach by using a bile acid to potentially reduce inflammation and improve gut health. Most treatments for pouchitis focus on controlling bacterial overgrowth, but UDCA could target the condition's underlying causes by altering bile acid composition. Researchers are excited about UDCA because it might offer a new option for patients whose pouchitis doesn't respond well to antibiotics, providing relief with a different mechanism of action.

What evidence suggests that ursodeoxycholic acid might be an effective treatment for pouchitis?

Research has shown that ursodeoxycholic acid (UDCA) can benefit individuals with conditions like ulcerative colitis. One study found that combining UDCA with another treatment significantly reduced symptoms, as measured by the Mayo score, which assesses disease severity. Another study suggested that UDCA might work by affecting certain immune system components involved in inflammation. Additionally, UDCA has been found to lower the risk of colorectal cancer and other complications in some patients with ulcerative colitis. Overall, these findings suggest that UDCA could help manage inflammation and improve quality of life for individuals with pouchitis. Participants in this trial will receive UDCA to evaluate its effectiveness specifically for pouchitis in ulcerative colitis patients with antibiotic-refractory or antibiotic-dependent pouchitis. ^{1 2 6 7 8}

Who Is on the Research Team?

Sidhartha Sinha, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

Adults over 18 with a history of pouchitis after ileal pouch-anal anastomosis for ulcerative colitis, who have chronic antibiotic refractory or dependent pouchitis. They must show increased stool frequency and have evidence of disease through endoscopy and histology. Pregnant women, those allergic to UDCA, using certain medications or with significant other diseases are excluded.

Inclusion Criteria

My pouchitis hasn't improved with antibiotics or needs continuous antibiotics.

My internal exam shows significant inflammation.

My tests show signs of disease.

Exclusion Criteria

I regularly use NSAIDs for pain or inflammation.

My pancreas does not digest food properly.

Infections to cytomegalovirus or Clostridium Difficile

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ursodeoxycholic acid (UDCA) 300 mg two times daily for 10 weeks to treat pouchitis

10 weeks

Visits at baseline, week 6, and week 10

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ursodeoxycholic Acid (UDCA)

Trial Overview The trial is testing whether the drug ursodeoxycholic acid (UDCA) can reduce inflammation in patients with active antibiotic refractory or dependent pouchitis by altering bile acids in the intestine. The study will assess if UDCA improves inflammatory markers and quality of life.

How Is the Trial Designed?

Group I: ursodiol (ursodeoxycholic acid, UDCA) Experimental Treatment 1 Intervention

ursodiol (ursodeoxycholic acid, UDCA) 300 mg two times daily for 10 weeks to treat pouchitis in ulcerative colitis patients with antibiotic refractory or antibiotic dependent pouchitis

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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]

UDCA-glutamate (Glu) significantly enhances the delivery of ursodeoxycholic acid (UDCA) to the colon compared to standard UDCA, as shown in a study with Fisher rats over 5 days, leading to higher amounts of UDCA found in feces.

The conjugation of UDCA to glutamic acid reduces its absorption in the small intestine, suggesting that UDCA-Glu could be a promising pro-drug for improving treatment outcomes in colonic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new amino acid derivative of ursodeoxycholate, (N-L-Glutamyl)-UDCA (UDCA-Glu), to selectively release UDCA in the colon. Asciutti, S., Castellani, D., Nardi, E., et al.[2013]

In a study involving 24 healthy subjects, the Canadian Ursofalk tablets showed significantly better bioavailability of ursodeoxycholic acid (UDCA) compared to other formulations, with higher mean area under the curve (AUC) and peak serum concentration (Cmax).

The Canadian UDCA tablets also had a shorter time to reach peak concentration (Tmax), indicating that they are absorbed more quickly than the capsule formulations, which may enhance their effectiveness in treating conditions like primary biliary cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of four ursodeoxycholic acid preparations. Williams, CN., Al-Knawy, B., Blanchard, W.[2019]

Ursodeoxycholic acid (UDCA) significantly reduces mucosal damage in a rat model of colitis induced by trinitrobenzene sulfonic acid (TNB), showing effectiveness in both acute and acute/chronic inflammation scenarios.

Treatment with UDCA led to improved body weight gain in rats with colitis, indicating a potential benefit in overall health during intestinal inflammation recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis. Kullmann, F., Arndt, H., Gross, V., et al.[2013]

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]

In a placebo-controlled trial with 15 healthy volunteers, taking 900 mg/day of ursodeoxycholic acid (UDCA) significantly altered fecal bile acid composition, increasing levels of UDCA and lithocholic acid (LCA) while decreasing primary and secondary bile acids.

Despite these changes in bile acid composition, UDCA did not affect the cytolytic activity of fecal water, suggesting that UDCA supplementation does not provide a protective effect against colorectal cancer in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in bile acid composition and effect on cytolytic activity of fecal water by ursodeoxycholic acid administration: a placebo-controlled cross-over intervention trial in healthy volunteers. van Gorkom, BA., van der Meer, R., Boersma-van Ek, W., et al.[2019]

In a phase III trial involving 1285 participants, UDCA treatment showed a non-significant 12% reduction in overall colorectal adenoma recurrence compared to placebo, suggesting a potential benefit.

More importantly, UDCA significantly reduced the recurrence of high-grade dysplastic adenomas by 39%, indicating its potential role in preventing progression to colorectal cancer, especially in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. Alberts, DS., Martínez, ME., Hess, LM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8265401/

Clinical effects of ursodeoxycholic acid on patients with ... Mayo score in patients of the UDCA + Mesalazine group were significantly decreased from medians of 8.5 at baseline to 2.0 at post-treatment week ...

2. journals.lww.com journals.lww.com/sjga/fulltext/2021/27030/clinical_effects_of_ursodeoxycholic_acid_on.6.aspx

Clinical effects of ursodeoxycholic acid on patients with... Clinical effects of ursodeoxycholic acid on patients with ulcerative colitis may improve via the regulation of IL-23-IL-17 axis and the changes of the ...

3. gastrojournal.org gastrojournal.org/article/S0016-5085(03)00070-2/fulltext

Ursodeoxycholic acid as a chemopreventive agent in ... Our placebo-controlled study showed a 74% reduction in the risk for development of colorectal neoplasia in patients with UC and PSC who were treated with UDCA.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/12671884/

Ursodeoxycholic acid as a chemopreventive agent in ... Conclusions: UDCA significantly decreases the risk for developing colorectal dysplasia or cancer in patients with UC and PSC. Publication types. Clinical Trial ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01088607

Safety and Efficacy Study of Ursodeoxycholic Acid Therapy ... Pediatric PSC patients already receiving UDCA therapy will enter a four-phase trial consisting of baseline data collection (phase I, 4 weeks), 50% reduction in ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576912003608

Dose-dependent antiinflammatory effect of ... Oral administration of ursodeoxycholic acid was able to ameliorate experimental colonic inflammation. This occurred only at a relatively high dose (50 mg/kg day) ...

7. frontiersin.org frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1302998/full

Lactobacillus acidophilus and its metabolite ... Lactobacillus acidophilus (LA) is a common clinical probiotic that improves ulcerative colitis (UC) by restoring intestinal immune balance.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12436379/

Adverse events of ursodeoxycholic acid: a real-world ... A total of 1,651 AEs were identified to be associated with UDCA. Common AEs consistent with the drug insert included diarrhea or loose stools, ...