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Trial of High-dose Urso in Primary Sclerosing Cholangitis

Primary Purpose

Primary Sclerosing Cholangitis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ursodeoxycholic Acid
Placebo
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring Urso, PSC

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Chronic cholestatic disease of at least six months' duration. Serum alkaline phosphatase at least 1 ½ times the upper limits of normal. Retrograde, operative, percutaneous, or magnetic resonance cholangiography demonstrating intrahepatic and/or extrahepatic biliary duct obstruction, beading, or narrowing consistent with PSC within one year of the study entry. Liver biopsy in the previous one year which is available for review and compatible with the diagnosis of PSC. Compatible biopsy features include fibrous cholangitis, ductopenia with periportal inflammation and biliary fibrosis.

Sites / Locations

  • Mayo Clinic
  • Mayo Clinic
  • Mayo Clinic
  • St. Louis University
  • University of Nebraska Medical Center
  • Medical College of Virginia
  • University of Washington

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Ursodeoxycholic acid

Arm Description

Placebo tablet that is identical (size, color, etc) to experimental ursodeoxycholic acid tablet.

Ursodeoxycholic acid 28-30 mg/kg/day

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Failure
Treatment failure was defined as death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma, or progression to cirrhosis

Secondary Outcome Measures

Number of Deaths
Death at any time up to 5 years
Number of Participants Who Have a Liver Transplantation
Liver transplantation at any time up to 5 years
Number of Participants Meeting Minimal Listing Criteria for Liver Transplantation
Meeting minimal listing criteria for liver transplantation at any time up to 5 years. Minimal listing criteria are defined as a MELD score of 14 or higher. The Model For End-Stage Liver Disease (MELD) is a numeric score with a range of 6 to 40, where a higher score means worse liver disease.
Number of Participants Who Developed Cholangiocarcinoma
Development of cholangiocarcinoma at any time up to 5 years
Number of Participants Who Developed Varices
Development of esophogeal and/or gastric varices
Number of Participants Who Developed Cirrhosis
Development of cirrhosis based on liver biopsy
Alkaline Phosphatase at 12 Months
Alkaline phosphatase divided by the upper limit of normal
Alkaline Phosphatase at 24 Months
Alkaline phosphatase divided by the upper limit of normal
Alkaline Phosphatase at 36 Months
Alkaline phosphatase divided by the upper limit of normal
Aspartate Aminotransferase at 12 Months
Aspartate aminotransferase at divided by the upper limit of normal
Aspartate Aminotransferase at 24 Months
Aspartate aminotransferase at divided by the upper limit of normal
Aspartate Aminotransferase at 36 Months
Aspartate aminotransferase at divided by the upper limit of normal
Bilirubin at 12 Months
Bilirubin divided by the upper limit of normal
Bilirubin at 24 Months
Bilirubin divided by the upper limit of normal
Bilirubin at 36 Months
Bilirubin divided by the upper limit of normal

Full Information

First Posted
April 21, 2003
Last Updated
April 7, 2021
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00059202
Brief Title
Trial of High-dose Urso in Primary Sclerosing Cholangitis
Official Title
Multicentered Randomized Trial of High-dose Urso in Primary Sclerosing Cholangitis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
DSMB reviewed interim analysis and terminated the study due to futility.
Study Start Date
July 2002 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multicenter, randomized, controlled trial of high dose ursodiol versus placebo for patients with primary sclerosing cholangitis (PSC). The average duration of follow-up will be approximately five years with important clinical endpoints such as death, eligibility for liver transplantation, changes in histology and cholangiogram as well as liver biochemistries and quality of life data collected.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
Urso, PSC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet that is identical (size, color, etc) to experimental ursodeoxycholic acid tablet.
Arm Title
Ursodeoxycholic acid
Arm Type
Experimental
Arm Description
Ursodeoxycholic acid 28-30 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Ursodeoxycholic Acid
Other Intervention Name(s)
UDCA
Intervention Description
Ursodeoxycholic Acid 28-30 mg/kg/day in divided doses
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo for Urso
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Failure
Description
Treatment failure was defined as death, transplantation, meeting minimal listing criteria, development of varices, cholangiocarcinoma, or progression to cirrhosis
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Number of Deaths
Description
Death at any time up to 5 years
Time Frame
5 years
Title
Number of Participants Who Have a Liver Transplantation
Description
Liver transplantation at any time up to 5 years
Time Frame
5 years
Title
Number of Participants Meeting Minimal Listing Criteria for Liver Transplantation
Description
Meeting minimal listing criteria for liver transplantation at any time up to 5 years. Minimal listing criteria are defined as a MELD score of 14 or higher. The Model For End-Stage Liver Disease (MELD) is a numeric score with a range of 6 to 40, where a higher score means worse liver disease.
Time Frame
5 years
Title
Number of Participants Who Developed Cholangiocarcinoma
Description
Development of cholangiocarcinoma at any time up to 5 years
Time Frame
5 years
Title
Number of Participants Who Developed Varices
Description
Development of esophogeal and/or gastric varices
Time Frame
5 years
Title
Number of Participants Who Developed Cirrhosis
Description
Development of cirrhosis based on liver biopsy
Time Frame
5 years
Title
Alkaline Phosphatase at 12 Months
Description
Alkaline phosphatase divided by the upper limit of normal
Time Frame
12 months
Title
Alkaline Phosphatase at 24 Months
Description
Alkaline phosphatase divided by the upper limit of normal
Time Frame
24 months
Title
Alkaline Phosphatase at 36 Months
Description
Alkaline phosphatase divided by the upper limit of normal
Time Frame
36 months
Title
Aspartate Aminotransferase at 12 Months
Description
Aspartate aminotransferase at divided by the upper limit of normal
Time Frame
12 months
Title
Aspartate Aminotransferase at 24 Months
Description
Aspartate aminotransferase at divided by the upper limit of normal
Time Frame
24 months
Title
Aspartate Aminotransferase at 36 Months
Description
Aspartate aminotransferase at divided by the upper limit of normal
Time Frame
36 months
Title
Bilirubin at 12 Months
Description
Bilirubin divided by the upper limit of normal
Time Frame
12 months
Title
Bilirubin at 24 Months
Description
Bilirubin divided by the upper limit of normal
Time Frame
24 months
Title
Bilirubin at 36 Months
Description
Bilirubin divided by the upper limit of normal
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Chronic cholestatic disease of at least six months' duration. Serum alkaline phosphatase at least 1 ½ times the upper limits of normal. Retrograde, operative, percutaneous, or magnetic resonance cholangiography demonstrating intrahepatic and/or extrahepatic biliary duct obstruction, beading, or narrowing consistent with PSC within one year of the study entry. Liver biopsy in the previous one year which is available for review and compatible with the diagnosis of PSC. Compatible biopsy features include fibrous cholangitis, ductopenia with periportal inflammation and biliary fibrosis.
Facility Information:
Facility Name
Mayo Clinic
City
Scottsdale
State/Province
Arizona
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
St. Louis University
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
Medical College of Virginia
City
Richmond
State/Province
Virginia
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19585548
Citation
Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, Harnois D, Jorgensen R, Petz J, Keach J, Mooney J, Sargeant C, Braaten J, Bernard T, King D, Miceli E, Schmoll J, Hoskin T, Thapa P, Enders F. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. 2009 Sep;50(3):808-14. doi: 10.1002/hep.23082.
Results Reference
result

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Trial of High-dose Urso in Primary Sclerosing Cholangitis

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