TUDCA as a Therapy for Ulcerative Colitis (UC)

NCT ID: NCT04114292

Last Updated: 2021-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-17

Study Completion Date

2022-07-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Ulcerative Colitis

Keywords

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Ulcerative Colitis tudca tauroursodeoxycholic acid

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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 Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Open-label study. All patients will receive TUDCA.

Study Groups

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TUDCA

1.75-2 grams daily in divided dosing

Group Type EXPERIMENTAL

Tauroursoursodeoxycholic acid, brand name Tudcabil

Intervention Type DRUG

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

Interventions

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Tauroursoursodeoxycholic acid, brand name Tudcabil

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

Intervention Type DRUG

Other Intervention Names

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Tudcabil

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Crohn's and Colitis Foundation

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Barnes-Jewish West County Hospital

Creve Coeur, Missouri, United States

Site Status RECRUITING

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Matthew A Ciorba, MD

Role: CONTACT

Phone: 3142730301

Email: [email protected]

Lulu Huang

Role: CONTACT

Phone: 3142730301

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 18775308 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24089213 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22275310 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23336977 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24577114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22733998 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17241871 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18054561 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18318598 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20228799 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40236400 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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201812101

Identifier Type: -

Identifier Source: org_study_id