The Role of Secondary Bile Acids in Intestinal Inflammation

Eligibility Criteria

• 1. Written informed consent;
• 2. Male or female subjects, ≥18 years of age who have undergone an ileal pouch-anal anastomosis (IPAA) for UC.
• 3. History of pouchitis
• 4. 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
• 5. Symptomatic disease (stool frequency):
• 6. Histology: evidence of disease.
• 7. Modified PDAI (mPDAI) score \>= 5. The mPDAI consists of the symptom (range: 0-6) and endoscopy (range: 0-6) subscores.
• 8. Must have chronic antibiotic refractory or antibiotic dependent pouchitis.
• 1. Lack of effective contraception Women of childbearing potential may not participate unless they are surgically sterile or are using adequate contraception.
• 2. Women who are pregnant or breastfeeding;
• 3. History of allergy or adverse event to UDCA;
• 4. Changes in dose to strong analgesia, such as opioid containing compounds within 4 weeks of the Screening Visit.
• 5. History of regular nonsteroidal anti-inflammatory drugs (NSAID) use.
• 6. 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.
• 7. 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.
• 8. 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.
• 9. Use of rectal compounds is not permitted; these agents must be discontinued at the Screening Visit.
• 10. 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.
• 11. 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.
• 12. Previous use of UDCA is permitted: treatment course must have completed at least 12 weeks prior to the Screening Visit.
• 13. 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.
• 14. Anastomotic stricture
• 15. Unable to undertake endoscopic evaluation
• 16. Faecal incontinence due to anal sphincter dysfunction
• 17. Infections to cytomegalovirus or Clostridium Difficile
• 18. Faecal transplantation within 12 weeks of screening
• 19. Intestinal malabsorption
• 20. Pancreatic maldigestion
• 21. Suspected irritable pouch syndrome
• 22. Cuffitis (inflammation of the anal mucosa). Subjects with active antibiotic refractory pouchitis as the predominant condition, but who also have cuffitis, may be enrolled
• 23. Crohn's disease of the pouch; defined as either: a) complex perianal or pouch fistula and/or b) extensive pre-pouch ileitis with deep ulceration
• 24. Subjects with a history of neoplastic disease except for basal cell carcinoma or nonmetastatic squamous cell carcinoma of the skin
• 25. Subjects who are receiving or have received nasogastric/nasoenteric bottle feeding, an elemental diet, or total parenteral nutrition within the 2 weeks prior to Day 1
• 26. Subjects with a history of clinically significant and/or persistent haematologic, renal, hepatic, metabolic, psychiatric, central nervous system, pulmonary or cardiovascular disease; which in the investigator's opinion, would exclude entry into the study
• 27. Subjects with any laboratory tests considered clinically significant at screening
• 28. Subjects who may be unavailable for the duration of the trial, likely to be noncompliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason including, for example, inability to retain an enema formulation
• 29. Pelvic sepsis should be excluded