The Role of Secondary Bile Acids in Intestinal Inflammation

NCT03724175 | Terminated Phase 2 FDA Drug

• 1 other identifier: IRB-47198
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ulcerative Colitis; Pouchitis

Keywords

Ulcerative Colitis; Pouchitis

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who achieve clinical response at week 10.

  Clinical response is defined as reduction of mPDAI score by \>=2 points.

  change from screening to end of treatment (10 weeks)

Secondary Outcomes (8)

• Proportion of subjects who achieve remission at week 10.

  change from screening at end of treatment (10 weeks)

• Proportion of subjects who achieve endoscopic response at week 10.

  change from screening at end of treatment (10 weeks)

• Proportion of subjects who achieve endoscopic remission at week 10.

  change from screening at end of treatment (10 weeks)

• Proportion of subjects with a stool frequency represented by a Mayo subscore of <1 at Week 10.

  change from screening at the end of treatment (10 weeks)

• Mean change in Cleveland Global Quality of Life (CGQL)

  change from screening, at week 6 and at end of treatment (10 weeks)

Study Arms (1)

ursodiol (ursodeoxycholic acid, UDCA)

EXPERIMENTAL

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

Drug: ursodiol (ursodeoxycholic acid, UDCA)

Interventions

ursodiol (ursodeoxycholic acid, UDCA) DRUG

ursodiol (ursodeoxycholic acid, UDCA) 300 mg two times daily for 10 weeks for UC pouchitis patients

Also known as: NDC 0591-3159-01 Ursodiol Capsules, USP 300 mg

ursodiol (ursodeoxycholic acid, UDCA)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent;
• Male or female subjects, ≥18 years of age who have undergone an ileal pouch-anal anastomosis (IPAA) for UC.
• History of pouchitis
• Documented evidence of active pouchitis, based on endoscopy, symptoms and histopathology, as follows:
• Endoscopic score \>=2 on the endoscopic component of a modified Mayo endoscopic score (where friability is scored as \>2) Note: the area within 1 cm of the pouch staple, or pouch suture line, is not considered evaluable
• Symptomatic disease (stool frequency):
• Subjects must demonstrate increased stool frequency compared to what is considered "normal" after their IPAA operation ("baseline"). Stool frequency must be an absolute value of \> 6 stools per day, and \> 3 stools per day above the post-IPAA "baseline". Note: The measurement of stool frequency will be a 7-day average rounded to the nearest integer. The most recent 7 days of data will be used to calculate the average.
• Histology: evidence of disease.
• Modified PDAI (mPDAI) score \>= 5. The mPDAI consists of the symptom (range: 0-6) and endoscopy (range: 0-6) subscores.
• Must have chronic antibiotic refractory or antibiotic dependent pouchitis.

You may not qualify if:

• Lack of effective contraception Women of childbearing potential may not participate unless they are surgically sterile or are using adequate contraception.
• The following contraceptive methods are acceptable: hormonal (eg oral, injection, transdermal patch, implant, cervical ring), barrier (eg condom or diaphragm with spermicidal agent), intrauterine system or intrauterine device. If hormonal contraceptives are used by female subjects, they must be established for 6 weeks before the first administration of test product. Male sterilization is considered an acceptable form of contraception if the appropriate post-vasectomy documentation (absence of sperm) is provided in the subject's medical notes. Sexual abstinence is considered acceptable if this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (eg calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Male subjects with female partners of child-bearing potential and female subjects who are neither surgically sterilized nor post-menopausal (defined as no menses for one year or a follicle-stimulating hormone value \> 40 IU/L) will be required to use effective contraception throughout the study and for 30 days after.
• Women who are pregnant or breastfeeding;
• History of allergy or adverse event to UDCA;
• Changes in dose to strong analgesia, such as opioid containing compounds within 4 weeks of the Screening Visit.
• History of regular nonsteroidal anti-inflammatory drugs (NSAID) use.
• Oral 5-aminosalicylate (5-ASA) compounds; exclude subjects who have discontinued or changed doses of oral 5-ASA within 4 weeks of the Screening Visit.
• Oral budesonide \> 6.0 mg/day is not permitted; exclude subjects who have received budesonide for \< 6 weeks, or who have changed doses of budesonide within 4 weeks of the Screening Visit.
• Oral steroids other than budesonide: exclude subjects who exceed a daily dose of 15 mg prednisolone or equivalent, who have received oral steroids for \< 6 weeks, or who have changed dose within 4 weeks of the Screening Visit.
• Use of rectal compounds is not permitted; these agents must be discontinued at the Screening Visit.
• Immunosuppressant therapy (azathioprine, 6- mercaptopurine, methotrexate, cyclosporin); exclude subjects who have received treatment for \< 12 weeks, or who have changed doses within 8 weeks of the Screening Visit.
• Biological agents (Anti-tumour necrosis factor (anti - TNF) therapy, vedolizumab and / or ustekinumab); exclude subjects who have received biological agents for \<6 months prior to the screening visit, or who changed doses of the biological agent within 6 months prior to the screening visit.
• Previous use of UDCA is permitted: treatment course must have completed at least 12 weeks prior to the Screening Visit.
• All other agents targeted to pouchitis, including experimental agents, must have been discontinued at least 8 weeks prior to the Screening Visit, or for a period equivalent to 5 half-lives (t1⁄2) of the agent (whichever is longer) It is acceptable to recruit subjects who remain on optimised, stable doses of oral 5-ASA, oral steroids (below the doses stipulated above) and immunosuppressants.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (1)

• Weingarden AR, Chen C, Zhang N, Graiziger CT, Dosa PI, Steer CJ, Shaughnessy MK, Johnson JR, Sadowsky MJ, Khoruts A. Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection. J Clin Gastroenterol. 2016 Sep;50(8):624-30. doi: 10.1097/MCG.0000000000000427.

  PMID: 26485102 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative; Pouchitis

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases; Ileitis; Enteritis; Ileal Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Sidhartha Sinha, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst Prof-Med Ctr Line

Study Record Dates

• First Submitted: October 12, 2018
• First Posted: October 30, 2018
• Study Start: August 26, 2019
• Primary Completion: March 2, 2026
• Study Completion: March 2, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)