Clinical Research of Tapering UDCA in PBC Patients with a Complete Response (UDCA PBC)

Clinical Research of Tapering Ursodeoxycholic Acid in Primary Biliary Cholangitis Patients with a Complete Response

This study explores the feasibility of the reducing medication regimen for Ursodeoxycholic Acid(UDCA) in the treatment of primary biliary cholangitis. The participants will be distributed randomly into two experimental groups and one control group. The two experimental groups will receive reduced dosage of UDCA at different level, while the control group will receive standard dosage of UDCA. The effect of therapy will be evaluated every three months.

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: ursodeoxycholic acid

Detailed Description

Primary biliary cholangitis is a chronic, progressive liver disease of autoimmune origin characterized by nonpurulent destruction of intrahepatic ductule, lymphatic infiltration of portal area and long-term intrahepatic cholestasis leading to liver fibrosis and cirrhosis in absence of treatment. The diagnosis is made in the presence of antimitochondrial antibodies (AMA) coupled with an increase in alkaline phosphatase (ALP), a histologic confirmation being mandatory only in seronegative cases or overlap syndrome. Treatment is based on ursodeoxycholic acid (UDCA) and obeticholic acid, which are proved effective in improving biochemical index and preventing disease progression. While obeticholic acid is only approved in USA and Canada, UDCA seem to be the only choice for PBC patients in China. Study has shown that liver function improvement can be expected in six to nine months when patients receive standard dosage( 13 -15mg/kg/d) of UDCA. Recovery of liver function takes two years in 20% of patients ,and five years in 15% to 35% of patients. Lifetime medication is recommended among patients with good respond to UDCA, while the high cost has placed great burden on patients as well as the medical service system. Exploration of the reducing medication regimen of UDCA among stable PBC patients is of great significance under this circumstance. In our study, the 90 recruited PBC patients with a complete response will be distributed randomly into two experimental groups and one control group. The two experimental groups will receive reduced dosage of UDCA at 10mg/Kg and 5mg/Kg respectively, while the control group will receive standard 13-15mg/Kg dosage of UDCA. The effect of therapy will be evaluated every three months, which includes assessment of symptoms, life quality, disease progression, complete blood count, urinalysis, liver biochemical markers (ALT, AST, ALP, GGT, TBIL, DBIL, TP, ALB), blood lipid (CHO, TG, LDL, HDL), immunoglobulins, ESR, AMA, liver morphology and cirrhosis degree, along with peripheral T lymphocyte subpopulations and cytokines test.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Li Wang; Phone Number: 8613801175089; Email: wangli2221@sina.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Li Wang
    • Contact: Li Wang; Phone Number: 8613801175089; Email: wangli2221@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Satisfied the diagnostic criteria of PBC by the AASLDin 2000;
• Age≥18 years
• Clinical stage 2 and 3 (i.e. abnormal liver function and symptomatic phase);
• Patients with improved liver biochemical index( ALP and AST≤1.5× upper limit of normal, with a normal bilirubin level) after 6 to 12 months treatment of UDCA;
• Informed consent obtained.

Exclusion Criteria:

• Overlapped with other liver diseases (such as HBV, HCV, alcoholic cirrhosis, etc.) or serum ALT, AST more than 2 ULN;
• Decompensation of liver function (Child grade B/C);
• Complicated with important organ failure (such as renal insufficiency), serious infection or other serious complications;
• Pregnancy, preparation for pregnancy or pregnancy Lactation, psychiatric subjects, etc.;
• Participating in other clinical trials or participated in other clinical trials in three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10mg/Kg UDCA; Patients will receive a reduced dosage of 10mg/Kg UDCA orally everyday.	Drug: ursodeoxycholic acid; The two experimental groups will receive reduced dosage of UDCA at 10mg/Kg and 5mg/Kg everyday respectively, while the control group will receive standard dosage of UDCA.The treatment duration will be at least one year.; Other Names: UDCA
Experimental: 5mg/Kg UDCA; Patients will receive a reduced dosage of 5mg/Kg UDCA orally everyday.	Drug: ursodeoxycholic acid; The two experimental groups will receive reduced dosage of UDCA at 10mg/Kg and 5mg/Kg everyday respectively, while the control group will receive standard dosage of UDCA.The treatment duration will be at least one year.; Other Names: UDCA
Active Comparator: standard 13-15mg/Kg UDCA; Patients will receive standard dosage of 13-15mg/Kg UDCA everyday.	Drug: ursodeoxycholic acid; The two experimental groups will receive reduced dosage of UDCA at 10mg/Kg and 5mg/Kg everyday respectively, while the control group will receive standard dosage of UDCA.The treatment duration will be at least one year.; Other Names: UDCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence rate of primary biliary cholangitis	Liver biochemical markers (AST and ALP in U/L, TBIL in umol/L) that restored to normal increase(bilirubin>1xULN,ALP≥1.5X ULN, AST≥1.5XULN) again is considered to be PBC recurrence according to the Paris II criteria. The rate of recurrence will be described in percent.	change from baseline to month3,6,9,12.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Li Wang, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 27, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: ursodeoxycholic acid; reducing medication regimen
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: ZS-2237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: within 6 months after the trial complete
• IPD Sharing Access Criteria: IPD will be shared by Excel within six months after the trial complete with the public
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No