TUDCA as a Therapy for Ulcerative Colitis (UC)

NCT04114292 | Completed Phase 1 FDA Drug

• 1 other identifier: 201812101
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; tudca; tauroursodeoxycholic acid

Outcome Measures

Primary Outcomes (1)

• Determine the effect of TUDCA treatment on ER stress in colon biopsy tissues from subjects with symptomatic ulcerative colitis

  Change in ER stress markers as measured by expression of X box binding protein-1 (XBP1), Binding immunoglobulin protein (BIP) and Eukaryotic Translation Initiation Factor 2A (eIF2a) in colon biopsy tissues before and after 6 weeks of TUDCA treatment.

  Baseline and post 6 weeks of TUDCA treatment

Secondary Outcomes (3)

• Monitoring of UC patients for TUDCA safety and tolerability: Adverse events

  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)

• Change ulcerative colitis disease activity based on Total Mayo Score

  Baseline and post 6 weeks of TUDCA treatment

• Change in inflammation on histology by Goebes index

  Baseline and post 6 weeks of TUDCA treatment

Study Arms (1)

TUDCA

EXPERIMENTAL

1.75-2 grams daily in divided dosing

Drug: Tauroursoursodeoxycholic acid, brand name Tudcabil

Interventions

Tauroursoursodeoxycholic acid, brand name Tudcabil DRUG

Dosed in capsules containing 250 or 500mg of TUDCA for a total dose of 1.75-2g/day

Also known as: Tudcabil

TUDCA

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Crohn's and Colitis Foundation: collaborator
• Washington University School of Medicine: lead

Study Sites (3)

Barnes-Jewish West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (11)

• Kaser A, Lee AH, Franke A, Glickman JN, Zeissig S, Tilg H, Nieuwenhuis EE, Higgins DE, Schreiber S, Glimcher LH, Blumberg RS. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease. Cell. 2008 Sep 5;134(5):743-56. doi: 10.1016/j.cell.2008.07.021.

  PMID: 18775308 BACKGROUND

• Adolph TE, Tomczak MF, Niederreiter L, Ko HJ, Bock J, Martinez-Naves E, Glickman JN, Tschurtschenthaler M, Hartwig J, Hosomi S, Flak MB, Cusick JL, Kohno K, Iwawaki T, Billmann-Born S, Raine T, Bharti R, Lucius R, Kweon MN, Marciniak SJ, Choi A, Hagen SJ, Schreiber S, Rosenstiel P, Kaser A, Blumberg RS. Paneth cells as a site of origin for intestinal inflammation. Nature. 2013 Nov 14;503(7475):272-6. doi: 10.1038/nature12599. Epub 2013 Oct 2.

  PMID: 24089213 BACKGROUND

• Cao SS, Song B, Kaufman RJ. PKR protects colonic epithelium against colitis through the unfolded protein response and prosurvival signaling. Inflamm Bowel Dis. 2012 Sep;18(9):1735-42. doi: 10.1002/ibd.22878. Epub 2012 Jan 24.

  PMID: 22275310 BACKGROUND

• Cao SS, Zimmermann EM, Chuang BM, Song B, Nwokoye A, Wilkinson JE, Eaton KA, Kaufman RJ. The unfolded protein response and chemical chaperones reduce protein misfolding and colitis in mice. Gastroenterology. 2013 May;144(5):989-1000.e6. doi: 10.1053/j.gastro.2013.01.023. Epub 2013 Jan 18.

  PMID: 23336977 BACKGROUND

• Cao SS, Wang M, Harrington JC, Chuang BM, Eckmann L, Kaufman RJ. Phosphorylation of eIF2alpha is dispensable for differentiation but required at a posttranscriptional level for paneth cell function and intestinal homeostasis in mice. Inflamm Bowel Dis. 2014 Apr;20(4):712-22. doi: 10.1097/MIB.0000000000000010.

  PMID: 24577114 BACKGROUND

• Wang S, Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol. 2012 Jun 25;197(7):857-67. doi: 10.1083/jcb.201110131.

  PMID: 22733998 BACKGROUND

• Shkoda A, Ruiz PA, Daniel H, Kim SC, Rogler G, Sartor RB, Haller D. Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Gastroenterology. 2007 Jan;132(1):190-207. doi: 10.1053/j.gastro.2006.10.030. Epub 2006 Oct 21.

  PMID: 17241871 BACKGROUND

• Hu S, Ciancio MJ, Lahav M, Fujiya M, Lichtenstein L, Anant S, Musch MW, Chang EB. Translational inhibition of colonic epithelial heat shock proteins by IFN-gamma and TNF-alpha in intestinal inflammation. Gastroenterology. 2007 Dec;133(6):1893-904. doi: 10.1053/j.gastro.2007.09.026. Epub 2007 Sep 25.

  PMID: 18054561 BACKGROUND

• Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, Taupin D, Thornton DJ, Png CW, Crockford TL, Cornall RJ, Adams R, Kato M, Nelms KA, Hong NA, Florin TH, Goodnow CC, McGuckin MA. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 2008 Mar 4;5(3):e54. doi: 10.1371/journal.pmed.0050054.

  PMID: 18318598 BACKGROUND

• 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.

  PMID: 20228799 BACKGROUND

• Lamm V, Huang K, Deng R, Cao S, Wang M, Soleymanjahi S, Promlek T, Rodgers R, Davis D, Nix D, Escudero GO, Xie Y, Chen CH, Gremida A, Rood RP, Liu TC, Baldridge MT, Deepak P, Davidson NO, Kaufman RJ, Ciorba MA. Tauroursodeoxycholic Acid (TUDCA) Reduces ER Stress and Lessens Disease Activity in Ulcerative Colitis. medRxiv [Preprint]. 2025 Apr 4:2025.04.02.25322684. doi: 10.1101/2025.04.02.25322684.

  PMID: 40236400 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label study. All patients will receive TUDCA.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 25, 2019
• First Posted: October 3, 2019
• Study Start: January 17, 2019
• Primary Completion: June 7, 2022
• Study Completion: June 7, 2022
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)