RECRUITING

The Role of Secondary Bile Acids in Intestinal Inflammation

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

The Role of Secondary Bile Acids in Intestinal Inflammation

Quick Facts

Study Start:2019-08-26

Study Completion:2050-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03724175

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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

Inclusion Criteria

Exclusion 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

Contacts and Locations

Study Contact

Sidhartha Sinha, MD

CONTACT

6507365555

sidsinha@stanford.edu

Aida Habtezion, MD

CONTACT

6507365555

aida.habtezion@stanford.edu

Principal Investigator

Sidhartha Sinha, MD

PRINCIPAL_INVESTIGATOR

Stanford University

Study Locations (Sites)

Stanford University

Stanford, California, 94305

United States

Collaborators and Investigators

Sponsor: Stanford University

Sidhartha Sinha, MD, PRINCIPAL_INVESTIGATOR, Stanford University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-08-26

Study Completion Date2050-12-31

Study Record Updates

Study Start Date2019-08-26

Study Completion Date2050-12-31

Terms related to this study

Keywords Provided by Researchers

Ulcerative Colitis
Pouchitis

Additional Relevant MeSH Terms

Ulcerative Colitis
Pouchitis