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TUDCA as a Therapy for Ulcerative Colitis (UC) (TUDCA)

Primary Purpose

Ulcerative Colitis

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tauroursoursodeoxycholic acid, brand name Tudcabil

About this trial

This is an interventional health services research trial for Ulcerative Colitis focused on measuring Ulcerative Colitis, tudca, tauroursodeoxycholic acid

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Barnes-Jewish West County HospitalRecruiting
Barnes-Jewish HospitalRecruiting
Washington University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TUDCA

Arm Description

1.75-2 grams daily in divided dosing

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Monitor and define TUDCA safety/tolerability in this population through frequent monitoring and symptom assessment as detailed in the study procedures. Adverse events will be categorized according to CTCAE v5.0 criteria and grading.

Change ulcerative colitis disease activity based on Total Mayo Score

The Mayo Ulcerative colitis score is an aggregate of individual parameters evaluating rectal bleeding, stool frequency, endoscopic severity and physicians global assessment. Each of these subscores has a range from 0-3 where 3 is worse. a total score can range from 0 to 12 with 0 being in remission and 12 representing the most severe disease. As this is a secondary endpoint in a small trial, patients total scores (out of 12) will be compared from baseline to week 6 using a paired students t test. Mayo score reference is Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987;317:1625-9.

Change in inflammation on histology by Goebes index

The Geboes histology index is a reproducible grading scale for histological assessment of inflammation in ulcerative colitis. This is a six grade classification system for inflammation which can also be fine tuned within each grade. The grades are: 0, structural change only; 1, chronic inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4, crypt destruction; and 5, erosions or ulcers. As this is a secondary endpoint in a small trial, patients total scores (out of 20) will be compared from baseline to week 6 using a paired students t test. Higher scores represent more severe disease. The reference for the Geboes index is "Geboes K, Riddell R, Ost A, et al. A reproducible grading scale for histological assessment of inflammation in ulcerative colitis. Gut 2000;47:404-9."

Full Information

NCT ID

NCT04114292

First Posted

September 25, 2019

Last Updated

December 21, 2021

Sponsor

Washington University School of Medicine

Collaborators

Crohn's and Colitis Foundation

1. Study Identification

Unique Protocol Identification Number

NCT04114292

Brief Title

TUDCA as a Therapy for Ulcerative Colitis (UC)

Acronym

TUDCA

Official Title

A Phase I Open Label Study of the Efficacy and Safety of Tudca in Ulcerative Colitis

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Recruiting

Study Start Date

January 17, 2019 (Actual)

Primary Completion Date

July 31, 2022 (Anticipated)

Study Completion Date

July 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

Collaborators

Crohn's and Colitis Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ulcerative Colitis

Keywords

Ulcerative Colitis, tudca, tauroursodeoxycholic acid

7. Study Design

Primary Purpose

Health Services Research

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

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.

Masking

None (Open Label)

Masking Description

Open-label study. All patients will receive TUDCA.

Allocation

N/A

Enrollment

13 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

TUDCA

Arm Type

Experimental

Arm Description

1.75-2 grams daily in divided dosing

Intervention Type

Drug

Intervention Name(s)

Tauroursoursodeoxycholic acid, brand name Tudcabil

Other Intervention Name(s)

Tudcabil

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and post 6 weeks of TUDCA treatment

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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)

Title

Change ulcerative colitis disease activity based on Total Mayo Score

Description

Time Frame

Baseline and post 6 weeks of TUDCA treatment

Title

Change in inflammation on histology by Goebes index

Description

Time Frame

Baseline and post 6 weeks of TUDCA treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Matthew A Ciorba, MD

Phone

3142730301

mciorba@wustl.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Lulu Huang

Phone

3142730301

luluhuang@wustl.edu

Facility Information:

Facility Name

Barnes-Jewish West County Hospital

City

Creve Coeur

State/Province

Missouri

ZIP/Postal Code

63141

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matthew A Ciorba, MD

Facility Name

Barnes-Jewish Hospital

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matthew A Ciorba, MD

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matthew A Ciorba, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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18775308

Citation

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Citation

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Citation

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PubMed Identifier

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Citation

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Citation

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TUDCA as a Therapy for Ulcerative Colitis (UC)

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