Clinical Research of UCDA Reducing Medication Regimen in Stable PBC (UCDA PBC)

Clinical Research of Reducing Medication Regimen for Ursodeoxycholic Acid in Treatment of Stable Primary Biliary Cholangitis

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 patients of refractory PBC will be distributed randomly into two experimental groups and one control group. The two experimental groups will receive reduced dosage of UDCA at 250mg bid and 250mg qd respectively, while the control group will receive standard 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 (Anticipated): 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; Phone Number: 8613801175089; Email: wangli2221@sina.com
    • Principal Investigator: li wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Satisfied the diagnostic criteria of PBC by the AASLDin 2000;
• Aged 18-65 years old;
• Clinical stage 2 and 3 (i.e. abnormal liver function and symptomatic phase);
• Patients with improved liver biochemical index(i.e. bilirubin≤17μmol/L, ALP≤3ULN, and AST≤2ULN) for at least 6 months 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);
• Combined with other autoimmune diseases;
• 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.;
• Combined with tumor;
• 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: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ursodeoxycholic acid 250mg bid; Patients will receive a reduced dosage of ursodeoxycholic acid 250mg orally twice a day.	Drug: ursodeoxycholic acid; The two experimental groups will receive reduced dosage of UDCA at 250mg bid and 250mg qd respectively, while the control group will receive standard dosage of UDCA.The treatment duration will be five years.; Other Names: UDCA
Experimental: ursodeoxycholic acid 250mg qd; Patients will receive a reduced dosage of ursodeoxycholic acid 250mg orally once a day.	Drug: ursodeoxycholic acid; The two experimental groups will receive reduced dosage of UDCA at 250mg bid and 250mg qd respectively, while the control group will receive standard dosage of UDCA.The treatment duration will be five years.; Other Names: UDCA
Active Comparator: ursodeoxycholic acid standard dosage; Patients will receive standard dosage of ursodeoxycholic acid 250mg orally three times a day.	Drug: ursodeoxycholic acid; The two experimental groups will receive reduced dosage of UDCA at 250mg bid and 250mg qd respectively, while the control group will receive standard dosage of UDCA.The treatment duration will be five years.; 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, BIL in umol/L) that restored to normal increase(bilirubin>17μmol/L,ALP>3 ULM, AST>2 ULN) again is considered to be PBC recurrence. The rate of recurrence will be described in percent.	change from baseline to month3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60

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): March 21, 2020
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

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): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: ursodeoxycholic acid; reducing medication regimen
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; 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; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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