Clinical trial NCT04114292: TUDCA as a Therapy for Ulcerative Colitis (UC)
Official title: A Phase I Open Label Study of the Efficacy and Safety of Tudca in Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
tudca
tauroursodeoxycholic acid
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2019-10-03
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Determine the effect of TUDCA treatment on colon inflammation including ER stress in colon biopsy tissues from subjects with symptomatic ulcerative colitis. Secondary: Measure the safety, tolerance and efficacy of TUDCA treatment in symptomatic ulcerative colitis.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This is a Phase I open label study examining the efficacy and safety of TUDCA (tauroursodeoxycholic acid) in ulcerative colitis treatment.

Detailed description: TUDCA (tauroursodeoxycholic acid) is a dietary supplement that has shown to reduce cellular stress related to inflammation. In this Phase I study, patients with active ulcerative colitis will be receive TUDCA for six weeks. Safety and tolerability will be assessed. Efficacy will be assessed using ulcerative colitis disease activity measurements as well as markers of intestinal inflammation before and after treatment. The overall goal of this project is to determine TUDCA can provide a new therapeutic option with a desirable safety profile for patients with ulcerative colitis focused on the inflamed intestinal epithelium.

Eligibility criteria: Inclusion Criteria:

* Ages Eligible for Study: 18 Years to 65 Years;
* Confirmed ulcerative colitis disease through radiographic, endoscopic and/or histologic criteria;
* Confirmed with active ulcerative colitis (defined as a complete Mayo score ≥ 5 with endoscopic subscore of ≥ 1) See Appendix for Mayo Score using recent adaptation to include any friability on endoscopy to be scored as "2".
* On a stable dose of medications for inflammatory bowel disease (IBD) (i.e. no change in medication within 4 weeks of study enrollment) and not planning to initiate new medication other than TUDCA.

Exclusion Criteria:

* Those that received other chemical chaperone therapies in the 3 months prior to screening;
* Individuals accompanied by gallstones, other intestinal disorders or cancers, or any possible cholestatic pathologies that could alter the enterohepatic circulation of the bile acids, including previous cholecystectomy or short bowel syndrome;
* Subjects with alcohol or drug abuse within the recent year;
* Serious heart, lung, kidney, digestive, nervous, mental, or autoimmune diseases
* Those with plans for abdominal surgery;
* Those unable or unwilling to provide informed consent or failure to comply with the test requirements;
* Pregnant, lactating women;
* Those receiving or planning to receive medicines that inhibit the absorption of the bile acids in the intestine;
* All female subjects must have birth control and not plan to become pregnant during the study. As TUDCA may interfere in the absorption of oral contraceptives, the acceptable methods of birth control should include abstinence or 2 of the following intrauterine device (IUD-with or without local hormone release), diaphragm, spermicides, cervical cap, contraceptive sponge, and /or condoms.
* Subjects with baseline liver transamines (AST or ALT) \> 1.5 X the upper limit of normal.
* Patients with complete biliary obstruction and known hypersensitivity or intolerance to TUDCA or any of the components of Tudcabil (or to other bile acids).
* Patients with moderate-to-severe hepatic impairment.
* Evidence of worsening liver function based on the 2 initial laboratory values used to establish the baseline.

Primary outcomes:
measure: Determine the effect of TUDCA treatment on ER stress in colon biopsy tissues from subjects with symptomatic ulcerative colitis
timeFrame: Baseline and post 6 weeks of TUDCA treatment
Secondary outcomes:
measure: Monitoring of UC patients for TUDCA safety and tolerability: Adverse events
timeFrame: Every 2 weeks after starting TUDCA until 2 weeks after completing 6 weeks of TUDCA treatment. (i.e. study points weeks 2, 4, 6 and 8)
measure: Change ulcerative colitis disease activity based on Total Mayo Score
timeFrame: Baseline and post 6 weeks of TUDCA treatment
measure: Change in inflammation on histology by Goebes index
timeFrame: Baseline and post 6 weeks of TUDCA treatment
Other outcomes:
Locations:
city: Creve Coeur
country: United States
facility: Barnes-Jewish West County Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
References:
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citation: McGovern DP, Gardet A, Torkvist L, Goyette P, Essers J, Taylor KD, Neale BM, Ong RT, Lagace C, Li C, Green T, Stevens CR, Beauchamp C, Fleshner PR, Carlson M, D'Amato M, Halfvarson J, Hibberd ML, Lordal M, Padyukov L, Andriulli A, Colombo E, Latiano A, Palmieri O, Bernard EJ, Deslandres C, Hommes DW, de Jong DJ, Stokkers PC, Weersma RK; NIDDK IBD Genetics Consortium; Sharma Y, Silverberg MS, Cho JH, Wu J, Roeder K, Brant SR, Schumm LP, Duerr RH, Dubinsky MC, Glazer NL, Haritunians T, Ippoliti A, Melmed GY, Siscovick DS, Vasiliauskas EA, Targan SR, Annese V, Wijmenga C, Pettersson S, Rotter JI, Xavier RJ, Daly MJ, Rioux JD, Seielstad M. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet. 2010 Apr;42(4):332-7. doi: 10.1038/ng.549. Epub 2010 Mar 14.