Ursodeoxycholic Acid for Pouchitis

Recruiting in Palo Alto (17 mi)

Overseen by Sidhartha Sinha, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Stanford University

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

Disqualifiers: Pregnancy, Allergy to UDCA, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The cause of Inflammatory bowel disease (IBD) is unknown, but intestinal bacteria-involved in the production of molecules that impact health-are widely accepted to play a key role. A significant proportion of IBD patients with pouches (surgically created rectums after the diseased colon is removed) continue to have inflammation similar to their previous disease. Only a few microbes are known to have the capability to modify primary bile acids (PBAs) made by the liver to secondary bile acids (SBAs). SBAs are some of the most common metabolites in the colon and play key roles in several diseases. In this study the investigators will investigate if ursodeoxycholic acid (UDCA) may reduce inflammatory markers and improve quality of life (as assessed by validate survey) in those subjects with active antibiotic refractory or antibiotic dependent pouchitis.

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.

What data supports the effectiveness of the drug Ursodeoxycholic Acid (UDCA) for treating pouchitis?

Ursodeoxycholic Acid (UDCA) has been shown to inhibit the growth of Clostridium difficile, a bacteria that can cause infections like ileal pouchitis, and it is used to treat other conditions like primary sclerosing cholangitis and to prevent colorectal adenoma recurrence, suggesting it may help with pouchitis as well. ^{1 2 3 4 5}

Is ursodeoxycholic acid (UDCA) safe for humans?

Ursodeoxycholic acid (UDCA) is generally considered safe for humans and is used to treat various liver and gallbladder conditions. It has been described as a nontoxic bile acid and has been used in different medical treatments without significant safety concerns. ^{1 2 3 6 7}

How is the drug ursodeoxycholic acid (UDCA) unique for treating pouchitis?

Ursodeoxycholic acid (UDCA) is unique because it is a bile acid with immunomodulatory properties, which may help reduce inflammation in pouchitis. Unlike other treatments, UDCA is designed to be delivered specifically to the colon, potentially enhancing its effectiveness for this condition. ^{2 4 7 8 9}

Research Team

Sidhartha Sinha, MD

Principal Investigator

Stanford University

Eligibility Criteria

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.

I have a narrowing in my body where two sections were surgically connected.

Trial Timeline

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

Treatment Details

Interventions

• Ursodeoxycholic Acid (UDCA) (Bile Acid)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stanford University Stanford, CA

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2527

Patients Recruited

17,430,000+

References

1. 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] To test whether ursodeoxycholic acid (UDCA) is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile-associated ileal pouchitis.

2. 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] Ursodeoxycholic acid (UDCA) is a bile acid of industrial interest as it is used as an agent for the treatment of primary sclerosing cholangitis and the medicamentous, non-surgical dissolution of gallstones. Currently, it is prepared industrially from cholic acid following a seven-step chemical procedure with an overall yield of 99.5 mM 12-keto-UDCA within 4.5 h in a simple batch process on a liter scale.

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

Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. [2022] Ursodeoxycholic acid (UDCA) treatment is associated with a reduced incidence of colonic neoplasia in preclinical models and in patients with conditions associated with an increased risk for colon cancer. We conducted a phase III, double-blind placebo-controlled trial of UDCA to evaluate its ability to prevent colorectal adenoma recurrence.

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] Ursodeoxycholic acid (UDCA) is commonly used for the treatment of hepatobiliary disease. UDCA is a bile acid that can be detected in the bile acid assay. Its effect on biochemical analytes is unknown.

5. England 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. [2019] Ursodeoxycholic acid (UDCA) has been shown to affect membrane-damaging effects of bile acids in vitro and fecal bile acid composition in rats. This study evaluates the effect of UDCA on fecal bile acid composition and on cytolytic activity of fecal water in man to clarify the potential chemopreventive role of UDCA for colorectal cancer.

6. England pubmed.ncbi.nlm.nih.gov

Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis. [2013] Recently we observed that ursodeoxycholic acid (UDCA) ameliorates an experimental small intestinal inflammation induced by indomethacin in the rat. In this study, we have tested whether ursodeoxycholic acid also reduces mucosal damage in the bile-independent trinitrobenzene sulphonic acid (TNB) model of experimental colitis.

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

Adjuvant treatment with ursodeoxycholic acid may reduce the incidence of acute cardiac allograft rejection. [2013] The nontoxic bile acid, ursodeoxycholic acid (UDCA), is an effective drug for the treatment of different cholestatic conditions. Furthermore, an immunomodulatory capacity of UDCA has been reported in vitro, as well as in vivo, in different immune-mediated liver diseases and after liver transplantation.

8. England pubmed.ncbi.nlm.nih.gov

Bioavailability of four ursodeoxycholic acid preparations. [2019] Ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones.

9. Greece 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. [2013] Ursodeoxycholic acid (UDCA) is chemoprotective in animal models of colon cancer but results from clinical trials have been less impressive probably because UDCA is rapidly absorbed in the small intestine and little reaches the colon. UDCA-glutamate (Glu), a novel bile acid, was synthesized with the objective of utilizing peptide bond cleavage by brush border enzymes to enhance delivery of UDCA to the colon.